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Tan C, Qin G, Wang QQ, Li KM, Zhou YC, Yao SK. Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer. World J Gastrointest Oncol 2024; 16:2971-2987. [PMID: 39072170 PMCID: PMC11271786 DOI: 10.4251/wjgo.v16.i7.2971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 11/10/2023] [Revised: 03/08/2024] [Accepted: 05/15/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM To identify serum protein biomarkers for the early screening of AA and CRC. METHODS We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.
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Affiliation(s)
- Chang Tan
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Geng Qin
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Qian-Qian Wang
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Kai-Min Li
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Yuan-Chen Zhou
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Shu-Kun Yao
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Fu F, Yu Y, Zou B, Long Y, Wu L, Yin J, Zhou Q. Role of actin-binding proteins in prostate cancer. Front Cell Dev Biol 2024; 12:1430386. [PMID: 39055653 PMCID: PMC11269120 DOI: 10.3389/fcell.2024.1430386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/10/2024] [Accepted: 06/25/2024] [Indexed: 07/27/2024] Open
Abstract
The molecular mechanisms driving the onset and metastasis of prostate cancer remain poorly understood. Actin, under the control of actin-binding proteins (ABPs), plays a crucial role in shaping the cellular cytoskeleton, which in turn supports the morphological alterations in normal cells, as well as the invasive spread of tumor cells. Previous research indicates that ABPs of various types serve distinct functions, and any disruptions in their activities could predispose individuals to prostate cancer. These ABPs are intricately implicated in the initiation and advancement of prostate cancer through a complex array of intracellular processes, such as severing, linking, nucleating, inducing branching, assembling, facilitating actin filament elongation, terminating elongation, and promoting actin molecule aggregation. As such, this review synthesizes existing literature on several ABPs linked to prostate cancer, including cofilin, filamin A, and fascin, with the aim of shedding light on the molecular mechanisms through which ABPs influence prostate cancer development and identifying potential therapeutic targets. Ultimately, this comprehensive examination seeks to contribute to the understanding and management of prostate diseases.
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Affiliation(s)
| | | | | | | | | | | | - Qing Zhou
- Department of Andrology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
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Cao Z, Guan M, Cheng C, Wang F, Jing Y, Zhang K, Jiao J, Ruan L, Chen Z. KIF20B and MET, hub genes of DIAPHs, predict poor prognosis and promote pancreatic cancer progression. Pathol Res Pract 2024; 254:155046. [PMID: 38266456 DOI: 10.1016/j.prp.2023.155046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 01/24/2023] [Revised: 06/13/2023] [Accepted: 06/19/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND The DIAPHs (DIAPH1, DIAPH2, and DIAPH3) are members of the diaphanous subfamily of the formin family. KIF20B and MET, hub genes of DIAPHs, play crucial roles in cytoskeletal remodeling, cell migration, and adhesion. However, their combined prognostic and treatment value in pancreatic adenocarcinoma (PC) warrants further investigation. METHODS Multiomics analysis tools were used to comprehensively assess the genomic expression and prognostic value of KIF20B and MET in PC. Immune cell infiltration, functional enrichment, single-cell RNA-seq (scRNA) analysis, potential therapeutic drugs, and nomograms were established and analyzed. CCK-8 levels, transwell assay, Co-IP assay, mass spectrometry, and western blotting were performed to assess the role of KIF20B and MET as modulators of β-catenin and Lactate Dehydrogenase A (LDHA) in vitro. Xenograft tumor models were used to evaluate the anti-tumor effects in vivo. RESULTS DIAPHs, KIF20B, and MET were overexpressed and functioned as poor prognostic markers of PC. Immunoinfiltration analysis revealed that pDC and NK cells were enriched with low expression levels of KIF20B and MET, whereas Th2 cells were enriched with high expression levels of these two genes. The copy number variations (CNVs) in KIF20B and MET were positively correlated with B cell and CD4 + T cell infiltration. Immunological checkpoints NT5E and CD44 were positively correlated with KIF20B and MET expression. Moreover, the nomogram constructed based on KIF20B and MET demonstrated predictive value for overall survival. scRNA-Seq analysis indicated that KIF20B and MET were enriched in endothelial, malignant, B, T, and CD8 + T cells, which correlated with glycolysis and the epithelial-mesenchymal transition (EMT). The interactions of KIF20B and MET with β-catenin and LDHA were verified by Co-IP assay and mass spectrometry. Knockdown of KIF20B and MET downregulates β-catenin and LDHA in vitro. Furthermore, dual knockdown of KIF20B and MET exhibited a synergistic suppressive effect on PC progression in vitro and in vivo. CONCLUSION DIAPHs, KIF20B, and MET are promising candidates for the prognosis and treatment of PC. More importantly, downregulation of KIF20B and MET inhibited pancreatic cancer progression by regulating LDHA and EMT.
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Affiliation(s)
- Zhangqi Cao
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Mingwei Guan
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Chienshan Cheng
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Fengjiao Wang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Yanhua Jing
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Ke Zhang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Juying Jiao
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Linjie Ruan
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Zhen Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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Foda AAM, El-Hawary AK, Elnaghi K, Eldehna WM, Enan ET. Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence. Tumour Biol 2024; 46:1-11. [PMID: 38728194 DOI: 10.3233/tub-230038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). CONCLUSIONS Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.
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Affiliation(s)
- Abd AlRahman Mohammad Foda
- Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Department of Pathology, General Medicine Practice Program, Batterjee Medical College, Jeddah, Saudi Arabia
| | - Amira Kamal El-Hawary
- Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Pathology Department, Horus Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Khaled Elnaghi
- Medical Oncology Unit, Internal Medicine Faculty of Medicine, Oncology Centre, Mansoura, Egypt
- Medical Oncology Department, Oncology Center King Abdullah Medical City, Makkah, Saudi Arabia
| | - Wesal M Eldehna
- Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Department of Oncology, International Medical Center, Jeddah, Saudi Arabia
| | - Eman T Enan
- Department of Anatomic Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Venditti M, Arcaniolo D, De Sio M, Minucci S. Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders. Int J Mol Sci 2021; 22:ijms22158094. [PMID: 34360857 PMCID: PMC8347498 DOI: 10.3390/ijms22158094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/11/2021] [Revised: 07/22/2021] [Accepted: 07/23/2021] [Indexed: 02/07/2023] Open
Abstract
Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.
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Affiliation(s)
- Massimo Venditti
- Dipartimento di Medicina Sperimentale, Sez, Fisiologia Umana e Funzioni Biologiche Integrate “F. Bottazzi”, Università degli Studi della Campania “Luigi Vanvitelli”, Via Costantinopoli 16, 80138 Napoli, Italy
- Correspondence: (M.V.); (S.M.)
| | - Davide Arcaniolo
- Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Napoli, Italy; (D.A.); (M.D.S.)
| | - Marco De Sio
- Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Napoli, Italy; (D.A.); (M.D.S.)
| | - Sergio Minucci
- Dipartimento di Medicina Sperimentale, Sez, Fisiologia Umana e Funzioni Biologiche Integrate “F. Bottazzi”, Università degli Studi della Campania “Luigi Vanvitelli”, Via Costantinopoli 16, 80138 Napoli, Italy
- Correspondence: (M.V.); (S.M.)
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DIAPH1 regulates chromosomal instability of cancer cells by controlling microtubule dynamics. Eur J Cell Biol 2021; 100:151156. [PMID: 33689956 DOI: 10.1016/j.ejcb.2021.151156] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/18/2021] [Revised: 02/17/2021] [Accepted: 02/22/2021] [Indexed: 12/14/2022] Open
Abstract
Chromosomal instability (CIN) is a hallmark of cancer, resulting from misalignment and missegregation of chromosomes during meta- and anaphase, due to non-precise regulation of spindle-MT dynamics. Diaphanous Related Formin 1 (DIAPH1) is an actin nucleator and also binds microtubule (MT) with high affinity. In this study, we analyzed the role of DIAPH1 in regulation of spindle MT-dynamics and CIN in HT29 and HCT-116 colorectal cancer (CRC) cells. Our data show that down-regulation of DIAPH1 in these cell lines decreased spindle-MT speed by 50 % and the fraction of cells with misaligned and missegregated chromosomes was significantly increased. Furthermore, in HCT-116 DIAPH1 depleted cells deviation of chromosome number was elevated and the number of cells with micronuclei and cytosolic DNA was increased in both DIAPH1-knock down cell lines. In line with these results, database analysis revealed a significant correlation with low DIAPH1 mRNA expression and aneuploidy. Thus, DIAPH1 is substantially involved in the control of CIN in CRC cells. Since in vitro, DIAPH1 directly increased MT-polymerization, we assume that DIAPH1 controls CIN by regulating spindle-MT dynamics.
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A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas. Cell Commun Signal 2020; 18:61. [PMID: 32276641 PMCID: PMC7146875 DOI: 10.1186/s12964-020-00550-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 06/30/2019] [Accepted: 03/11/2020] [Indexed: 12/16/2022] Open
Abstract
Background Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined. Methods MiRNA expression profiling was performed across various cell types isolated from skin and cSCCs. Microarray results were confirmed by qPCR and by an optimized in situ hybridization protocol. Functional impact of overexpression or knock-out of a dysregulated miRNA was assessed in migration and 3D-spheroid assays. Sample-matched transcriptome data was generated to support the identification of disease relevant miRNA targets. Results Several miRNAs were identified as dysregulated in cSCCs compared to control skin. These included the metastasis-linked miR-10b, which was significantly upregulated in primary cell cultures and in archival biopsies. At the functional level, overexpression of miR-10b conferred the stem cell-characteristic of 3D-spheroid formation capacity to keratinocytes. Analysis of miR-10b downstream effects identified a novel putative target of miR-10b, the actin- and tubulin cytoskeleton-associated protein DIAPH2. Conclusion The discovery that miR-10b mediates an aspect of cancer stemness – that of enhanced tumor cell adhesion, known to facilitate metastatic colonization – provides an important avenue for future development of novel therapies targeting this metastasis-linked miRNA.
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Abstract
Formin homology proteins (formins) are a highly conserved family of cytoskeletal remodeling proteins that are involved in a diverse array of cellular functions. Formins are best known for their ability to regulate actin dynamics, but the same functional domains also govern stability and organization of microtubules. It is thought that this dual activity allows them to coordinate the activity of these two major cytoskeletal networks and thereby influence cellular architecture. Golgi ribbon assembly is dependent upon cooperative interactions between actin filaments and cytoplasmic microtubules originating both at the Golgi itself and from the centrosome. Similarly, centrosome assembly, centriole duplication, and centrosome positioning are also reliant on a dialogue between both cytoskeletal networks. As presented in this chapter, a growing body of evidence suggests that multiple formin proteins play essential roles in these central cellular processes.
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Affiliation(s)
- John Copeland
- Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
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Asadipooya K, Lankarani KB, Raj R, Kalantarhormozi M. RAGE is a Potential Cause of Onset and Progression of Nonalcoholic Fatty Liver Disease. Int J Endocrinol 2019; 2019:2151302. [PMID: 31641351 PMCID: PMC6766674 DOI: 10.1155/2019/2151302] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 01/30/2019] [Revised: 08/05/2019] [Accepted: 08/26/2019] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Fatty liver is a rising global health concern, significantly increasing the burden of health care cost. Nonalcoholic fatty liver disease (NAFLD) has a correlation with metabolic syndrome and its complications. METHOD We reviewed the literature regarding the mechanisms of developing NAFLD through AGE-RAGE signaling. RESULTS NAFLD, metabolic syndrome, and production of advanced glycation end-products (AGEs) share many common risk factors and appear to be connected. AGE induces production of the receptor for AGE (RAGE). AGE-RAGE interaction contributes to fat accumulation in the liver leading to inflammation, fibrosis, insulin resistance, and other complications of the fatty liver disease. The immune system, especially macrophages, has an important defense mechanism against RAGE pathway activities. CONCLUSION Soluble form of RAGE (sRAGE) has the capability to reduce inflammation by blocking the interaction of AGE with RAGE. However, sRAGE has some limitations, and the best method of usage is probably autotransplantation of transfected stem cells or monocytes, as a precursor of macrophages and Kupffer cells, with a virus that carries sRAGE to alleviate the harmful effects of AGE-RAGE signaling in the settings of fatty liver disease.
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Affiliation(s)
- Kamyar Asadipooya
- Division of Endocrinology and Molecular Medicine, Department of Medicine, University of Kentucky, Lexington, KY, USA
| | - Kamran B. Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Rishi Raj
- Division of Endocrinology and Molecular Medicine, Department of Medicine, University of Kentucky, Lexington, KY, USA
| | - Mohammadreza Kalantarhormozi
- Endocrinology and Internal Medicine, The Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran
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DIAPH3 promoted the growth, migration and metastasis of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling. Mol Cell Biochem 2017; 438:183-190. [PMID: 28795316 DOI: 10.1007/s11010-017-3125-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/07/2017] [Accepted: 07/17/2017] [Indexed: 12/21/2022]
Abstract
The enhanced ability of cancer cell migration and metastasis is the major cause for the cancer-related death of hepatocellular carcinoma (HCC). Better understanding the mechanisms for the motility of cancer cells will benefit the treatment. Diaphanous-related formin 3 (DIAPH3) has been reported to regulate the motility of cells by remodeling the cytoskeleton. However, the mechanism through which DIAPH3 regulated the motility of cancer cells remains largely unknown. In this study, we have shown that the expression of DIAPH3 was up-regulated in HCC. DIAPH3 positively regulated the growth, migration, colony formation, epithelia mesenchymal transition, and metastasis of HCC cells. Mechanically, DIAPH3 activated the beta-catenin/TCF signaling by binding HSP90 and disrupting the interaction between GSK3beta and HSP90. Taken together, our study demonstrated the oncogenic activity of DIAPH3 in the progression of HCC and suggested that PDIAPH3 might be a therapeutic target.
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