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Luo Y, Wei W, Huang Y, Li J, Qin W, Hao Q, Ye J, Zhang Z, Liang Y, Xiao X, Cai Y. A new signature associated with anoikis predicts the outcome and immune infiltration in nasopharyngeal carcinoma. Discov Oncol 2025; 16:123. [PMID: 39913001 PMCID: PMC11802990 DOI: 10.1007/s12672-025-01869-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 02/03/2025] [Indexed: 02/07/2025] Open
Abstract
BACKGROUND Previous studies have confirmed the phenomenon of anoikis resistance in nasopharyngeal carcinoma (NPC). Nevertheless, the prognostic significance of anoikis-related genes (ARGs) in NPC remains incompletely understood. This study aimed to create a predictive risk score using an ARGs signature for NPC patients and to investigate how this score relates to clinicopathologic features and immune infiltration in the tumor microenvironment. METHODS By using data from the Gene Expression Omnibus (GEO) database, we employed machine learning methods to discover prognostic ARGs and create a risk score. Key gene expression levels were validated through real-time PCR and immunohistochemical staining. RESULTS Three differentially expressed ARGs (CDC25C, E2F1 and RBL2) with prognostic value were identified by the intersection of multiple machine learning algorithms. A risk score based on t 3-ARG feature was developed to stratify NPC patients into two distinct risk groups using the optimal model, Random Survival Forest. NPC patients with high-risk scores experienced notably shorter progression-free survival in comparison to those with low-risk scores. Multivariate Cox regression analysis indicated that the risk score served as an independent prognostic factor. The time-dependent ROC and decision curve analyses demonstrated the risk model's strong predictive accuracy and clinical utility. The low-risk score group exhibited features indicative of early clinical stage, immune activation, high immune checkpoint gene's expression, and low Epstein-Barr virus gene's expression. Functional analysis revealed enrichment of immune-related pathways in the low-risk group. Patients with high-risk scores were discovered to be unlikely to benefit from immune checkpoint inhibitor treatment. Moreover, the expression of RBL2, E2F1, and CDC25C were significantly correlated with the expression of caspase family genes. Finally, the lower mRNA and protein expression of RBL2 were validated in NPC cell lines and tissues. CONCLUSIONS Our ARGs-based signature model shows promising results in predicting the prognosis of NPC patients and might be associated with immune cell infiltration.
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Affiliation(s)
- Yonglin Luo
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
| | - Wenyang Wei
- School of Clinical Medicine, Guilin Medical University, Guilin, China
| | - Yaxuan Huang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jun Li
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Weiling Qin
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Quanxiang Hao
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
| | - Jiemei Ye
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Zhe Zhang
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yushan Liang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xue Xiao
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yonglin Cai
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
- Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, China.
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Zhu X, Lin SQ, Xie J, Wang LH, Zhang LJ, Xu LL, Xu JG, Lv YB. Biomarkers of lymph node metastasis in colorectal cancer: update. Front Oncol 2024; 14:1409627. [PMID: 39328205 PMCID: PMC11424378 DOI: 10.3389/fonc.2024.1409627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 08/20/2024] [Indexed: 09/28/2024] Open
Abstract
Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.
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Affiliation(s)
- Xiao Zhu
- Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Shui-Quan Lin
- Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Jun Xie
- Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Li-Hui Wang
- Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Li-Juan Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ling-Ling Xu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jian-Guang Xu
- Department of Gastroenterology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
| | - Yang-Bo Lv
- Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China
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Roles of anoikis in colorectal cancer therapy and the assessment of anoikis-regulatory molecules as therapeutic targets. Pathol Res Pract 2023; 241:154256. [PMID: 36455367 DOI: 10.1016/j.prp.2022.154256] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 11/21/2022] [Accepted: 11/25/2022] [Indexed: 11/29/2022]
Abstract
Colorectal cancer (CRC) is a deadly malignancy and therapeutic approaches for CRC are evolving every day. Anoikis is a key mechanism for programmed cell death of cancer cells that undergo anchorage-independent growth at a different matrix than the one which is expected. Yet, anoikis is a less studied mechanism of cell death in comparison to other mechanisms such as apoptosis. Relating to this, resistance to anoikis among cancer cells remains critical for improved metastasis and survival in a new environment evading anoikis. Since CRC cells have the ability to metastasize from proximal sites to secondary organs such as liver and promote cancer in those distant sites, a clear knowledge of the mechanisms essential for anchorage-independent growth and subsequent metastasis is necessary to counteract CRC progression and spread. Therefore, the identification of novel drug candidates and studying the roles of anoikis in assisting CRC therapy using such drugs can prevent anchorage-independent cancer cell growth. Additionally, the identification of novel biomarkers or therapeutic targets seems essential for implementing superior therapy, impeding relapse among malignant cells and improving the survival rate of clinical patients. As there are no reviews published on this topic till date, anoikis as a mechanism of cell death and its therapeutic roles in CRC are discussed in this review. In addition, several molecules were identified as therapeutic targets for CRC.
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Raeisi M, Zehtabi M, Velaei K, Fayyazpour P, Aghaei N, Mehdizadeh A. Anoikis in cancer: The role of lipid signaling. Cell Biol Int 2022; 46:1717-1728. [DOI: 10.1002/cbin.11896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/10/2022] [Accepted: 08/11/2022] [Indexed: 12/20/2022]
Affiliation(s)
- Mortaza Raeisi
- Hematology and Oncology Research Center Tabriz University of Medical Sciences Tabriz Iran
| | - Mojtaba Zehtabi
- Hematology and Oncology Research Center Tabriz University of Medical Sciences Tabriz Iran
| | - Kobra Velaei
- Department of Anatomical Sciences Tabriz University of Medical Sciences Tabriz Iran
| | - Parisa Fayyazpour
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran
| | - Negar Aghaei
- Department of Psycology, Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran
- Imam Sajjad Hospital Tabriz Azad University Tabriz Iran
| | - Amir Mehdizadeh
- Hematology and Oncology Research Center Tabriz University of Medical Sciences Tabriz Iran
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Molecular mechanisms of tumour budding and its association with microenvironment in colorectal cancer. Clin Sci (Lond) 2022; 136:521-535. [PMID: 35445707 DOI: 10.1042/cs20210886] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/15/2022] [Accepted: 03/28/2022] [Indexed: 12/12/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Poor survival of CRC associated with the development of tumour metastasis led to the investigation of the potential biomarkers to predict outcomes in CRC patients. Tumour budding (TB) is a well-known independent prognostic marker for poor survival and disease metastasis. Therefore, it has been suggested that TB status is included in routine clinicopathological factors for risk assessment in CRC. In contrast with a vast majority of studies regarding the prognostic power of TB, there is no clear evidence pertaining to the underlying molecular mechanism driving this phenotype, or an understanding of TB relationship with the tumour microenvironment (TME). The aim of the present study is to present a comprehensive review of TB and tumour cell signalling pathways together with the cross-talk of immune cells that could drive TB formation in CRC.
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Xiang Z, He Q, Huang L, Xiong B, Xiang Q. Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation. Front Oncol 2022; 11:818869. [PMID: 35083162 PMCID: PMC8784696 DOI: 10.3389/fonc.2021.818869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 12/13/2021] [Indexed: 11/13/2022] Open
Abstract
Background Tumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer. Methods Tissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables. Results High-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713). Conclusion The combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.
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Affiliation(s)
- Zhenxian Xiang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
| | - Qiuming He
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
| | - Li Huang
- Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Xiong
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.,Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China
| | - Qingming Xiang
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.,Hubei Cancer Clinical Study Center, Wuhan, China.,Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, China
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Arai K, Iwasaki T, Ishimatsu H, Tsuchiya C, Kubota A, Sonoda A, Ohata K. A Case of Colonic Micropapillary Carcinoma with a High Frequency of Apoptosis. J Gastrointest Cancer 2021; 53:809-816. [PMID: 34302254 DOI: 10.1007/s12029-021-00674-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
Colorectal micropapillary carcinoma (MPC) exhibits aggressive biological characteristics, with empty spaces and reversed polarity, similar to the poorly differentiated clusters (PDCs) formed from detached cancer cells. Epithelial-mesenchymal transition, which is involved in the cancer cell acquisition of apoptosis resistance, is closely linked with histological findings of MPC, PDCs, and tumor buds (TBs), with MPC and TBs considered as apoptosis-resistant features. However, we encountered a case of colonic MPC with frequent apoptosis. We examined the case using immunohistochemistry. In many of the tumor glands (TGs) of the MPC, empty spaces and tumor cell detachment toward the gland interior were observed. Moreover, TG ruptures were scattered, with PDCs adjacent to them. Apoptosis occurred mainly at the TG and PDC peripheries in the middle and deep tumor layers, and transforming growth factor beta 1 (TGF-β1) positivity was evident in those tumor cells. Cells positive for apoptosis-related M30 were distributed mainly in the deep layer with a significant PDC and TB presence. However, apoptosis and M30 positivity were low in the TBs. Non-tumorous bud components, especially those in the deep layer, had poor ability to promptly acquire apoptosis resistance. No nuclear β-catenin positivity was found in any of the tumor cells. Apoptosis has the potential to reciprocally produce MPC, PDCs, and TBs, with TGF-β1 involvement.
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Affiliation(s)
- Kazumori Arai
- Department of Pathology, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan.
| | - Tomohiro Iwasaki
- Department of Pathology, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan
| | - Hisato Ishimatsu
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Chinatsu Tsuchiya
- Department of Pathology, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan
| | - Aki Kubota
- Department of Pathology, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan
| | - Akihiro Sonoda
- Department of Clinical Research, Shizuoka General Hospital, Shizuoka, Japan
| | - Ko Ohata
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
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Prill M, Karkucinska-Wieckowska A, Lebiedzinska-Arciszewska M, Morciano G, Charzynska A, Dabrowski M, Pronicki M, Pinton P, Grajkowska W, Wieckowski MR. Ras, TrkB, and ShcA Protein Expression Patterns in Pediatric Brain Tumors. J Clin Med 2021; 10:jcm10102219. [PMID: 34065573 PMCID: PMC8160917 DOI: 10.3390/jcm10102219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/13/2021] [Accepted: 05/17/2021] [Indexed: 11/16/2022] Open
Abstract
Numerous papers have reported altered expression patterns of Ras and/or ShcA proteins in different types of cancers. Their level can be potentially associated with oncogenic processes. We analyzed samples of pediatric brain tumors reflecting different groups such as choroid plexus tumors, diffuse astrocytic and oligodendroglial tumors, embryonal tumors, ependymal tumors, and other astrocytic tumors as well as tumor malignancy grade, in order to characterize the expression profile of Ras, TrkB, and three isoforms of ShcA, namely, p66Shc, p52Shc, and p46Shc proteins. The main aim of our study was to evaluate the potential correlation between the type of pediatric brain tumors, tumor malignancy grade, and the expression patterns of the investigated proteins.
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Affiliation(s)
- Monika Prill
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland; (M.P.); (M.L.-A.)
| | | | - Magdalena Lebiedzinska-Arciszewska
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland; (M.P.); (M.L.-A.)
| | - Giampaolo Morciano
- Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy; (G.M.); (P.P.)
| | - Agata Charzynska
- Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland; (A.C.); (M.D.)
| | - Michal Dabrowski
- Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland; (A.C.); (M.D.)
| | - Maciej Pronicki
- Department of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (A.K.-W.); (M.P.)
| | - Paolo Pinton
- Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy; (G.M.); (P.P.)
| | - Wieslawa Grajkowska
- Department of Pathology, The Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (A.K.-W.); (M.P.)
- Correspondence: (W.G.); (M.R.W.)
| | - Mariusz R. Wieckowski
- Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland; (M.P.); (M.L.-A.)
- Correspondence: (W.G.); (M.R.W.)
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Parisi E, Sorolla A, Montal R, González-Resina R, Novell A, Salud A, Sorolla MA. Prognostic Factors Involved in the Epithelial-Mesenchymal Transition Process in Colorectal Cancer Have a Preponderant Role in Oxidative Stress: A Systematic Review and Meta-Analysis. Cancers (Basel) 2020; 12:E3330. [PMID: 33187205 PMCID: PMC7697515 DOI: 10.3390/cancers12113330] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 11/06/2020] [Accepted: 11/09/2020] [Indexed: 12/12/2022] Open
Abstract
Epithelial-to-mesenchymal transition (EMT) is one of the most accepted mechanisms leading to metastasis, which is responsible for most of the cancer-related deaths. In order to identify EMT-related biomarkers able to predict clinical outcomes in colorectal cancer (CRC), a systematic review and meta-analysis of prognostic factors associated to overall survival (OS) and progression free survival (PFS) was conducted. The systematic literature search included studies from June 2014 to June 2019 available at PubMed and Scopus databases. Meta-analysis was performed for those markers appearing in minimum three works with a total number of 8656 participants. The rest were enlisted and subjected to functional enrichment. We identified nine clinical biomarkers and 73 EMT-related molecular biomarkers associated to OS and/or PFS in CRC. The significant enrichment of biomarkers found involved in cellular oxidoreductase activity suggests that ROS generation plays an active role in the EMT process. Clinical practice needs new biomarkers with a reliable prognostic value able to predict clinical outcomes in CRC. Our integrative work supports the role of oxidative stress in tumorigenesis and EMT progress highlighting the importance of deciphering this specific mechanism to get a better understanding of metastasis.
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Affiliation(s)
- Eva Parisi
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
| | - Anabel Sorolla
- Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA 6009, Australia;
- Centre for Medical Research, The University of Western Australia, Crawley, WA 6009, Australia
| | - Robert Montal
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
- Department of Medical Oncology, Arnau de Vilanova University Hospital, 25198 Lleida, Spain
| | - Rita González-Resina
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
| | - Anna Novell
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
| | - Antonieta Salud
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
- Department of Medical Oncology, Arnau de Vilanova University Hospital, 25198 Lleida, Spain
| | - Maria Alba Sorolla
- Research Group of Cancer Biomarkers, Biomedical Research Institute (IRBLleida), 25198 Lleida, Spain; (E.P.); (R.M.); (R.G.-R.); (A.N.); (A.S.)
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Abstract
Tumour budding is an emerging prognostic biomarker in colorectal cancer (CRC) and other solid cancers. Tumour buds are usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumour front. The prognostic value of tumour budding is now supported by a large body of evidence, whereas the utility of this phenotype as a predictive biomarker remains under investigation. The application of tumour budding indices in clinical practice requires a standardized scoring system that can be tailored to specific tumour types and clinical scenarios. In the context of CRC, tumour budding can be assessed according to the method agreed at the International Tumour Budding Consensus Conference (ITBCC) in 2016. Using the ITBCC scoring system, tumour budding is an independent predictor of lymph node metastasis in patients with pT1 CRC and of unfavourable survival in patients with stage II colon cancer. Regardless of the clinical scenario or tumour type, the assertion that 'the more tumour buds, the worse the clinical outcome' applies. In this Review, we provide an overview of tumour budding in solid cancers, highlighting the molecular and biological aspects of this phenomenon, including its associations with epithelial-mesenchymal transition and features of the tumour microenvironment. We also describe the available evidence demonstrating the value of tumour budding as a biomarker across various solid cancers.
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11
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Serafim Junior V, Fernandes GMDM, Oliveira-Cucolo JGD, Pavarino EC, Goloni-Bertollo EM. Role of Tropomyosin-related kinase B receptor and brain-derived neurotrophic factor in cancer. Cytokine 2020; 136:155270. [PMID: 32911446 DOI: 10.1016/j.cyto.2020.155270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 08/27/2020] [Indexed: 02/07/2023]
Abstract
The tropomyosin-related kinase B (TrkB) receptor is a member of the neurotrophic tyrosine kinase receptors family and, together with the brain-derived neurotrophic factor (BDNF), plays an important role in the development of breast cancer, lung cancer, neuroblastoma, colorectal cancer, leukemia, cervical cancer, gallbladder cancer, gastric cancer, kidney cancer, Ewing's sarcoma, esophageal cancer, and head and neck cancer. Overexpression of these two factors has been associated with increased processes involved in carcinogenesis, such as invasion, migration, epithelial-mesenchymal transition (EMT), angiogenesis, metastasis, cell proliferation, resistance to apoptosis, resistance to cell death due to loss of adhesion (anoikis), activation of cell proliferation pathways, regulation of tumor suppressor genes, and drug resistance, and is related to advanced clinical stage. Inhibition of the TrkB/BDNF axis using drugs in phase 1 studies, approved drugs, and small interfering RNA (siRNA) are promising strategies for the treatment of various malignant tumors in addition to increasing the sensitivity of cells resistant to chemotherapy, improving the effectiveness of drugs without increasing toxicity. Another factor related to poor cancer prognosis is the presence of cancer stem cells, having effects similar to the high expression of the TrkB/BDNF axis, on cancer. This review aimed to show the role of the TrkB/BDNF axis in several types of cancer, its possible use as a prognostic biomarker, the effects of inhibiting this axis, and its role in the cancer stem cells.
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Affiliation(s)
- Vilson Serafim Junior
- Genetics and Molecular Biology Research Unit (UPGEM), São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, São Paulo, Brazil
| | - Glaucia Maria de Mendonça Fernandes
- Genetics and Molecular Biology Research Unit (UPGEM), São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, São Paulo, Brazil
| | - Juliana Garcia de Oliveira-Cucolo
- Genetics and Molecular Biology Research Unit (UPGEM), São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, São Paulo, Brazil
| | - Erika Cristina Pavarino
- Genetics and Molecular Biology Research Unit (UPGEM), São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, São Paulo, Brazil
| | - Eny Maria Goloni-Bertollo
- Genetics and Molecular Biology Research Unit (UPGEM), São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, São Paulo, Brazil.
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Patankar M, Mattila T, Väyrynen JP, Klintrup K, Mäkelä J, Tuomisto A, Nieminen P, Mäkinen MJ, Karttunen TJ. Putative anoikis-resistant subpopulations in colorectal carcinoma: a marker of adverse prognosis. APMIS 2020; 128:390-400. [PMID: 32202676 DOI: 10.1111/apm.13041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 03/02/2020] [Indexed: 12/11/2022]
Abstract
Anoikis is a form of apoptosis induced when a cell loses contact with the extracellular matrix (ECM). Anoikis resistance is essential for metastasis formation, yet only detectable by in vitro experiments. We present a method for quantitation of putative anoikis-resistant (AR) subpopulations in colorectal carcinoma (CRC) and evaluate their prognostic significance. We studied 137 CRC cases and identified cell subpopulations with and without stromal or extracellular matrix (ECM) contact with hematoxylin-and-eosin-stained sections and immunohistochemistry for laminin and type IV collagen. Suprabasal cells of micropapillary structures and inner cells of cribriform and solid structures lacked both stromal contact and contact with ECM proteins. Apoptosis rate (M30) was lower in these subpopulations than in the other carcinoma cells, consistent with putative AR subpopulation. We determined the areal density of these subpopulations (number/mm2 tumor tissue), and their high areal density independently indicates low cancer-specific survival. In conclusion, we show evidence that subpopulations of carcinoma cells in micropapillary, cribriform, and solid structures are resistant to anoikis as shown by lack of ECM contact and low apoptosis rate. Abundance of these subpopulations is a new independent indicator of poor prognosis in CRC, consistent with the importance of anoikis resistance in the formation of metastasis.
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Affiliation(s)
- Madhura Patankar
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
| | - Taneli Mattila
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
| | - Juha P Väyrynen
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Kai Klintrup
- Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.,Department of Surgery, Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland
| | - Jyrki Mäkelä
- Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland.,Department of Surgery, Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland
| | - Anne Tuomisto
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
| | - Pentti Nieminen
- Medical Informatics and Data Analysis Research Group, University of Oulu, Oulu, Finland
| | - Markus J Mäkinen
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
| | - Tuomo J Karttunen
- Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.,Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
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13
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Maffeis V, Cappellesso R, Galuppini F, Guzzardo V, Zanon A, Cazzador D, Emanuelli E, Ventura L, Martini A, Fassina A. Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition. Virchows Arch 2020; 477:241-248. [PMID: 31980958 DOI: 10.1007/s00428-020-02748-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 12/23/2019] [Accepted: 01/08/2020] [Indexed: 12/26/2022]
Abstract
Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting. We selected 32 surgically resected specimens of non-mucinous/non-signet ring ITAC and evaluated them for TB according to the international recommendations developed for CRC. The expression of the EMT markers E-cadherin, ZEB1, ZEB2, SLUG, and SNAIL was evaluated by immunohistochemistry (IHC). Results were stratified using clinical and follow-up data (2/32 patients had metastatic disease and 4/32 died of disease). We observed TB in 13/32 (40.6%) ITAC cases including the 7 patients with relapse (p = 0.0005) and the 4 patients dead of disease (p = 0.02). Lymphovascular invasion was associated with TB (p = 0.008). Absence of TB was associated with low ZEB2 expression (p = 0.003). No other association with EMT markers emerged. Occupational exposure to wood and leather dust was not related to the presence of TB. TB interobserver concordance was substantial (proportion of agreement = 87%; Cohen's kappa = 0.73). This work suggests that TB is associated with a worse prognosis in ITAC, but our findings do not seem to support the involvement of EMT in this specific setting. Further larger studies are needed to address this point.
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Affiliation(s)
- Valeria Maffeis
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy.
| | - Rocco Cappellesso
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy
| | - Francesca Galuppini
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy
| | - Vincenza Guzzardo
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy
| | - Alessia Zanon
- Department of Neurosciences, Otorhinolaryngology Section, University of Padova, Padua, Italy
| | - Diego Cazzador
- Department of Neurosciences, Otorhinolaryngology Section, University of Padova, Padua, Italy.,Department of Neurosciences, Section of Human Anatomy, University of Padova, Padua, Italy
| | - Enzo Emanuelli
- Department of Neurosciences, Otorhinolaryngology Section, University of Padova, Padua, Italy
| | - Laura Ventura
- Department of Statistics, University of Padova, Padua, Italy
| | - Alessandro Martini
- Department of Neurosciences, Otorhinolaryngology Section, University of Padova, Padua, Italy
| | - Ambrogio Fassina
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy
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14
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Maffeis V, Nicolè L, Cappellesso R. RAS, Cellular Plasticity, and Tumor Budding in Colorectal Cancer. Front Oncol 2019; 9:1255. [PMID: 31803624 PMCID: PMC6877753 DOI: 10.3389/fonc.2019.01255] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 10/30/2019] [Indexed: 12/14/2022] Open
Abstract
The high morbidity and mortality of colorectal cancer (CRC) remain a worldwide challenge, despite the advances in prevention, diagnosis, and treatment. RAS alterations have a central role in the pathogenesis of CRC universally recognized both in the canonical mutation-based classification and in the recent transcriptome-based classification. About 40% of CRCs are KRAS mutated, 5% NRAS mutated, and only rare cases are HRAS mutated. Morphological and molecular correlations demonstrated the involvement of RAS in cellular plasticity, which is related to invasive and migration properties of neoplastic cells. RAS signaling has been involved in the initiation of epithelial to mesenchymal transition (EMT) in CRC leading to tumor spreading. Tumor budding is the morphological surrogate of EMT and features cellular plasticity. Tumor budding is clinically relevant for CRC patients in three different contexts: (i) in pT1 CRC the presence of tumor buds is associated with nodal metastasis, (ii) in stage II CRC identifies the cases with a prognosis similar to metastatic disease, and (iii) intratumoral budding could be useful in patient selection for neoadjuvant therapy. This review is focused on the current knowledge on RAS in CRC and its link with cellular plasticity and related clinicopathological features.
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Affiliation(s)
- Valeria Maffeis
- Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | - Lorenzo Nicolè
- Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
| | - Rocco Cappellesso
- Pathological Anatomy Unit, Padova University Hospital, Padova, Italy
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15
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Shen T, Cheng X, Xia C, Li Q, Gao Y, Pan D, Zhang X, Zhang C, Li Y. Erlotinib inhibits colon cancer metastasis through inactivation of TrkB-dependent ERK signaling pathway. J Cell Biochem 2019; 120:11248-11255. [PMID: 30719765 DOI: 10.1002/jcb.28400] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/24/2018] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
The distal metastasis is the main cause of death in patients with colon cancer. Tyrosine receptor kinase B (TrkB) and ERK signals may be the potential targets for the treatment of colon cancer metastasis. This study aims to investigate whether erlotinib inhibits distant metastasis of colon cancer by regulating TrkB and ERK signaling pathway. Human colon adenocarcinoma cell lines (SW480 and Caco-2) pretreated with exogenous C-X-C motif chemokine ligand 8 (CXCL8) were used to assess the suppressive effect of erlotinib on tumor metastasis, including anoikis, epithelial-mesenchymal transformation (EMT), migration, and invasion. Through TrkB overexpression, Akt suppression, and ERK suppression, the roles of TrkB, Akt, and ERK in erlotinib-induced metastasis inhibition of colon cancer cells were explored. The results showed that erlotinib alleviated CXCL8-induced metastasis of the colon cancer cells. Overexpression of TrkB in colon cancer cells eliminated the effect of erlotinib on anoikis, inhibition of EMT, migration, and invasion, and downregulation of p-ERK and p-Akt. Furthermore, the inhibition of ERK activation instead of Akt activation was found to participate in erlotinib-mediated metastasis resistance, including anoikis, inhibition of EMT, migration, and invasion. In conclusion, erlotinib inhibits colon cancer cell anoikis resistance, EMT, migration, and invasion by inactivating TrkB-dependent ERK signaling pathway.
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Affiliation(s)
- Tao Shen
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Xianshuo Cheng
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Cuifeng Xia
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Qiang Li
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yi Gao
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Dingguo Pan
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Xuan Zhang
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Ce Zhang
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Yunfeng Li
- Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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16
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Jiang L, Chen S, Zhao D, Yan J, Chen J, Yang C, Zheng G. MNX1 reduces sensitivity to anoikis by activating TrkB in human glioma cells. Mol Med Rep 2018; 18:3271-3279. [PMID: 30066929 PMCID: PMC6102707 DOI: 10.3892/mmr.2018.9329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 02/27/2018] [Indexed: 11/08/2022] Open
Abstract
Glioma is the most common type of malignant intracranial tumor in adults and is associated with the highest mortality rate. Although surgery, radiotherapy, chemotherapy and other treatment methods have progressed, the median survival of patients with glioma is only 14–15 months. Glioma cells are able to penetrate along blood vessels and invade into the surrounding normal brain tissue so that an overall resection of the tumor cannot be performed. In the process of metastasis, the resistance of cancer cells to anoikis has an important role. When tumor cells escape from their original environment, anoikis resistance aids their survival. In the present study, reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR), RT-quantitative PCR and western blotting demonstrated that the transcription factor, motor neuron and pancreas homeobox 1 (MNX1), was ectopically expressed in glioma cells compared with normal HUVEC-C human umbilical vein endothelial cells. Furthermore, its expression was higher in more malignant glioma cell lines (T98G and M059K) compared with the less malignant glioma cell line (U-87 MG) and normal HUVEC-C cells. An adhesion assay using fibronectin demonstrated that MNX1 and tyrosine kinase receptor B (TrkB) overexpression in HUVEC-C and U-87 MG cells reduced adhesion and forced them to suspend. Additionally, MNX1 and TrkB overexpression was demonstrated to increase the ability of cells to bypass anoikis. MNX1 and TrkB knockdown increased adhesion and promoted apoptosis after suspension. It was further demonstrated that MNX1 functioned as a transcription factor binding in the upstream regulatory region of TrkB to activate its expression. The results of the present study suggested that MNX1 may suppress the adhesion and apoptosis rates of tumor cells by activating TrkB. The results of the present study suggest that MNX1 may represent a novel therapeutic target for the treatment of gliomas.
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Affiliation(s)
- Lai Jiang
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Shaojun Chen
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Donggang Zhao
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Jun Yan
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Jiemin Chen
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Chunlin Yang
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
| | - Gang Zheng
- Department of Neurosurgery, The People's Hospital of China Three Gorges University, Yichang, Hubei 443000, P.R. China
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17
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Zhang C, Li X, Gao D, Ruan H, Lin Z, Li X, Liu G, Ma Z, Li X. The prognostic value of over-expressed TrkB in solid tumors: a systematic review and meta-analysis. Oncotarget 2017; 8:99394-99401. [PMID: 29245910 PMCID: PMC5725101 DOI: 10.18632/oncotarget.19561] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 07/11/2017] [Indexed: 01/17/2023] Open
Abstract
It is reported recently Tropomyosin-related receptor Kinase B (TrkB) plays key roles in the anoikis resistance during the processes of tumorigenesis and metastasis. However, its prognostic significance for clinical patients remains inconclusive. In order to establish a correct and practicable link between increased TrkB and prognostication of human solid tumors, a meta-analysis was performed in this article. A systematic literature research in the electronic databases PubMed, Embase and Web of Science was performed to identify eligible studies. A fixed-effects meta-analytical model was employed to correlate TrkB expression with OS, DFS and clinicopathological features. A total of 11 studies covering 1516 patients with various solid tumors were recruited in this meta-analysis. TrkB over-expression was associated with poorer OS and poorer DFS in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that TrkB over-expression was associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that TrkB over-expression in patients with solid tumors might be related to poor prognosis and serve as a potential predictive marker of poor clinicopathological prognosis factor.
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Affiliation(s)
- Chunze Zhang
- Department of Immunology, Tianjin Medical University, Tianjin, China.,Tianjin Union Medical Center, Tianjin, China
| | - Xiaoting Li
- Department of Immunology, Tianjin Medical University, Tianjin, China
| | - Dan Gao
- Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico, United States
| | - Haihua Ruan
- Tianjin Key Laboratory of Food Science and Biotechnology, College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China
| | - Zhenzhen Lin
- Department of Immunology, Tianjin Medical University, Tianjin, China
| | - Xiaobo Li
- Department of Immunology, Tianjin Medical University, Tianjin, China
| | - Guang Liu
- Tianjin Union Medical Center, Tianjin, China
| | - Zhicheng Ma
- Department of Gastrointestinal Surgery, Tianjin First Center Hospital, Tianjin, China
| | - Xichuan Li
- Department of Immunology, Tianjin Medical University, Tianjin, China
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18
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Li Y, Liu D, Cheng Z, Proksch P, Lin W. Cytotoxic trichothecene-type sesquiterpenes from the sponge-derived fungus Stachybotrys chartarum with tyrosine kinase inhibition. RSC Adv 2017. [DOI: 10.1039/c6ra26956g] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Bioassay-guided fractionation of a sponge associated fungus Stachybotrys chartarum resulted in the isolation of 15 trichothecene-based sesquiterpenes with inhibitory effects against tumor cell lines.
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Affiliation(s)
- Yong Li
- State Key Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- P. R. China
| | - Dong Liu
- State Key Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- P. R. China
| | - Zhongbin Cheng
- State Key Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- P. R. China
| | - Peter Proksch
- Institute of Pharmaceutical Biology and Biotechnology
- Heinrich-Heine University
- 40225 Duesseldorf
- Germany
| | - Wenhan Lin
- State Key Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- P. R. China
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19
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Akil H, Perraud A, Jauberteau MO, Mathonnet M. Tropomyosin-related kinase B/brain derived-neurotrophic factor signaling pathway as a potential therapeutic target for colorectal cancer. World J Gastroenterol 2016; 22:490-500. [PMID: 26811602 PMCID: PMC4716054 DOI: 10.3748/wjg.v22.i2.490] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Revised: 09/25/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death in western countries. Approximately one-quarter of newly diagnosed patients for CRC have metastases, and a further 40%-50% experience disease recurrence or develop metastases after all standard therapies. Therefore, understanding the molecular mechanisms involved in the progression of CRC and subsequently developing novel therapeutic targets is crucial to improve management of CRC and patients’ long-term survival. Several tyrosine kinase receptors have been implicated in CRC development, progression and metastasis, including epidermal growth factor receptor (EGFR) and vascular EGFR. Recently, tropomyosin-related kinase B (TrkB), a tyrosine kinase receptor, has been reported in CRC and found to clearly exert several biological and clinical features, such as tumor cell growth and survival in vitro and in vivo, metastasis formation and poor prognosis. Here we review the significance of TrkB and its ligand brain derived-neurotrophic factor in CRC. We focus on their expression in CRC tumor samples, and their functional roles in CRC cell lines and in in vivo models. Finally we discuss therapeutic approaches that can lead to the development of novel therapeutic agents for treating TrkB-expressing CRC tumors.
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20
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Computational Design of TrkB Peptide Inhibitors and Their Biological Effects on Ovarian Cancer Cell Lines. Int J Pept Res Ther 2016. [DOI: 10.1007/s10989-015-9510-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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21
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Dawson H, Lugli A. Molecular and pathogenetic aspects of tumor budding in colorectal cancer. Front Med (Lausanne) 2015; 2:11. [PMID: 25806371 PMCID: PMC4354406 DOI: 10.3389/fmed.2015.00011] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 02/25/2015] [Indexed: 12/20/2022] Open
Abstract
In recent years, tumor budding in colorectal cancer has gained much attention as an indicator of lymph node metastasis, distant metastatic disease, local recurrence, worse overall and disease-free survival, and as an independent prognostic factor. Tumor buds, defined as the presence of single tumor cells or small clusters of up to five tumor cells at the peritumoral invasive front (peritumoral buds) or within the main tumor body (intratumoral buds), are thought to represent the morphological correlate of cancer cells having undergone epithelial–mesenchymal transition (EMT), an important mechanism for the progression of epithelial cancers. In contrast to their undisputed prognostic power and potential to influence clinical management, our current understanding of the biological background of tumor buds is less established. Most studies examining tumor buds have attempted to recapitulate findings of mechanistic EMT studies using immunohistochemical markers. The aim of this review is to provide a comprehensive summary of studies examining protein expression profiles of tumor buds and to illustrate the molecular pathways and crosstalk involved in their formation and maintenance.
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Affiliation(s)
- Heather Dawson
- Clinical Pathology Division, Institute of Pathology, University of Bern , Bern , Switzerland ; Translational Research Unit, Institute of Pathology, University of Bern , Bern , Switzerland
| | - Alessandro Lugli
- Clinical Pathology Division, Institute of Pathology, University of Bern , Bern , Switzerland ; Translational Research Unit, Institute of Pathology, University of Bern , Bern , Switzerland
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