• Goose
• Polysaccharides of Atractylodes macrocephala Koidz
• Thymic involution
• Transcriptome analysis

• Acteoside
• Epithelial-mesenchymal transition
• Extracellular regulated kinases 1/2 pathway
• Liver cancer
• Schisandra chinensis lignans

• Epithelial-Mesenchymal Transition/drug effects
• Humans
• Lignans/pharmacology
• Schisandra/chemistry
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Animals
• Mice
• Cell Proliferation/drug effects
• MAP Kinase Signaling System/drug effects
• Phenols/pharmacology
• Glucosides/pharmacology
• Apoptosis/drug effects
• Cell Movement/drug effects
• Mice, Nude
• Cell Line, Tumor
• Chemokine CCL20/metabolism
• Chemokine CCL20/genetics
• Mice, Inbred BALB C
• Hep G2 Cells
• Multiomics
• Polyphenols

• 20194Y0202 Research Project of Shanghai Municipal Health Commission
• HKQ-ZYY-2021-33 Research project on traditional Chinese medicine of Hongkou District Health Commission
• SY-XKZT-2020-1014 Project of Discipline Promotion Program of Shanghai Fourth People's Hospital

• chemokine
• chemokine receptors
• hepatocellular carcinoma
• prognosis
• signature

• This study was supported by the National Natural Science Foundation of China
• Jiangxi Province Graduate Innovation Special Fund Project

• CCL20
• biomarker
• breast cancer
• immune infiltration
• interaction network
• therapeutic target

• Female
• Humans
• Breast Neoplasms/genetics
• Databases, Factual
• Monocytes
• Neutrophils
• Prognosis
• Biomarkers, Tumor/genetics
• Chemokine CCL20/genetics

• CC chemokine
• CC chemokine receptor
• Chemokine
• Inflammation
• Osteoarthritis

• Breast cancer
• Crosstalk
• Tumor microenvironment
• c-MYC

• dairy goat
• genetic diversity
• milk production traits
• population structure
• selective signal

• Animals
• Exosomes
• Leydig Cells
• Male
• Rats
• Seminiferous Tubules
• Sertoli Cells/physiology
• Testis/physiology

CCL20-CCR6 interactions promote colorectal cancer through direct effects on neoplastic epithelial cells and through modulating the tumor microenvironment. The mechanism of these effects on neoplastic epithelial cells is poorly understood. This study demonstrates that CCL20 induces secretion of hepatocyte growth factor (HGF) and phosphorylation of HGF’s cognate receptor c-Met in HT29 and HCT116 colorectal cancer cell lines both in concentration- and time-dependent manners. Similar to CCL20, HGF induces migration, autofeedback CCL20 secretion, and ERK1/2 phosphorylation in the colon cancer cells. CCL20-dependent ERK1/2 phosphorylation is blocked by HGF inhibition, and CCL20-dependent migration and CCL20 secretion are blocked by inhibition of HGF or ERK. Interestingly, unlike CCL20, HGF does not induce proliferation of colon cancer cells, and CCL20-dependent cell proliferation is not blocked by direct HGF inhibition. CCL20-dependent proliferation, however, is blocked by the multi-tyrosine kinase inhibitor crizotinib. Exploring this effect, it was found that CCL20 also induces production of MSP and phosphorylation of MSP’s receptor MSPR by the colorectal cancer cells. CCL20-dependent cell proliferation is inhibited by directly blocking MSP-MSPR interactions. Thus, CCL20-mediated migration and CCL20 secretion are regulated through a pathway involving HGF, c-Met, and ERK, while CCL20-mediated proliferation is instead regulated through MSP and its receptor MSPR.

• CCL20
• CCR6
• HGF
• MSP
• colorectal cancer

The immune response against cancer is generated by effector T cells, among them cytotoxic CD8⁺ T cells that destroy cancer cells and helper CD4⁺ T cells that mediate and support the immune response. This antitumor function of T cells is tightly regulated by a particular subset of CD4⁺ T cells, named regulatory T cells (Tregs), through different mechanisms. Even if the complete inhibition of Tregs would be extremely harmful due to their tolerogenic role in impeding autoimmune diseases in the periphery, the targeted blockade of their accumulation at tumor sites or their targeted depletion represent a major therapeutic challenge. This review focuses on the mechanisms favoring Treg recruitment, expansion and stabilization in the tumor microenvironment and the therapeutic strategies developed to block these mechanisms.

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4⁺ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

• proliferation
• recruitment
• regulatory T cells
• stability
• therapeutic targeting
• tumor microenvironment

• cancer stem cells
• preclinical research

• chemokine-chemokine receptor
• exosomeimmune suppression
• metabolism
• tumor-associated macrophages
• tyrosine kinase receptor

• Animals
• Disease Models, Animal
• Humans
• Immunotherapy/methods
• Mice
• Neoplasms/immunology
• Neoplasms/therapy
• Tumor Microenvironment/immunology
• Tumor-Associated Macrophages/immunology

• National Natural Science Foundation of China
• Guangdong Science and Technology Department
• Department of Education of Guangdong Province
• Science and Technology Planning Project of Guangdong Province

• Bone metastasis
• Breast cancer (BC)
• Chemokine
• Tumor immunity
• tumor microenvironment (TME)

Our previous study demonstrated that upregulation of multiple epidermal growth factor-like domains 11 (MEGF11) gene expression is involved in the mechanism by which recurrence of Triple Negative Breast Cancer (TNBC) occurs. Our aim was to elucidate the role of MEGF11 expression in TNBC cells, both in vitro and in vivo, and in human tissue. Following MEGF11 gene knockdown (∆MEGF11) or over-expression in MDA-MB-231 and MB-468 cells, cell growth and chemokine gene expression were evaluated. In vivo, tumour growth of implanted human TNBC cells and the number of circulating 4T1 mouse tumour cells were measured. There was a significant decrease in cell growth via inhibition of AKT, NF-kB, CREB and AP-1 activation in ∆MEGF11 MDA-MB-231 and 468 cells. This also resulted, in vivo, in a suppression of tumour growth and a decrease in the number of mouse circulating 4T1 breast cancer cells. Surprisingly, overexpression of MEGF11 upregulated the expression of various chemokines and proinflammatory cytokines via AKT activation, but there was no increase in cell proliferation. MEGF11 was found to cross-talk positively with IL-17A signalling. Patients with tumours that over-expressed MEGF11 had a poorer prognosis. We conclude that MEGF11 plays an important role in tumour survival and that overexpression of MEGF11 induces both a cytokine and a chemokine cascade, which will favour the tumour microenvironment in terms of distant metastasis. MEGF11 might be a potential therapeutic target for preventing TNBC recurrence.

• C-C chemokine ligand type 2 (CCL2)
• C-C chemokine receptor type 2 (CCR2)
• CCL2
• CCR2
• G protein-coupled receptor (GPCR)
• GTPase-activating protein (GAP)
• actin
• cell signaling
• chemokine
• cytoskeleton
• data-independent acquisition
• data-independent acquisition mass spectrometry (DIA-MS)
• guanine nucleotide exchange factor (GEF)
• mass spectrometry (MS)
• nuclear pore
• phosphoproteomics
• signaling networks

• Mesenchymal stem cells
• Metabolic syndrome
• Proteins
• Tumor necrosis factor
• mRNA

• R01 DK122734 NIDDK NIH HHS
• K08 DK106427 NIDDK NIH HHS
• R03 DK122137 NIDDK NIH HHS
• U01 DK104273 NIDDK NIH HHS
• R01 DK102325 NIDDK NIH HHS
• R01 DK120292 NIDDK NIH HHS

• Prostate cancer
• prognostic markers

• CCL20
• CCR6
• Cancer
• Chemokine
• Cytokine
• Dendritic cells (DCs)
• NF-κB
• Regulatory T cells (Tregs)
• T helper 17 cells (Th17 cells)
• Tumor microenvironment (TME)

Tumor-associated regulatory T cells (Tregs) are important effectors in the tumor microenvironment (TME), acting as accomplices in the promotion of tumor progression. Currently, the importance of removing the immunosuppressive activity in the TME has received its due attention, and Tregs have been focused on. The cytokine-receptor axes are among the essential signaling pathways in immunocytes, and tumor-associated Tregs are no exception. Therefore, manipulating cytokine-receptor pathways may be a promising effective strategy for treating various malignancies. Here, we summarize the classification, immunosuppressive mechanisms, existing immunotherapies, and potential biomarkers related to tumor-infiltrating Tregs to guide the development of effective cancer immunotherapies.

• Tregs
• biomarkers
• cancer immunotherapies
• chemokine receptors
• immune suppression

DEP domain containing 1 (DEPDC1) functions as an oncogene in hepatocellular carcinoma (HCC). However, the underlying mechanism of DEPDC1 remains largely unknown. The present study revealed that DEPDC1 knockdown inhibited HCC cell proliferation, colony formation and invasion in vitro and suppressed the growth of HCC xenografts in vivo. Furthermore, DEPDC1 overexpression promoted HCC cell proliferation, colony formation and invasion. DNA microarray, reverse transcription-quantitative-PCR and western blotting results demonstrated that DEPDC1 knockdown in Huh-7 significantly inhibited the expression of chemokine (C-C motif) ligand 20 (CCL20) and chemokine (C-C motif) receptor 6 (CCR6). In addition, the expression of CCL20 and CCR6 were upregulated in HCC tissues and cell lines, and were positively correlated with DEPDC1 expression. CCL20 or CCR6 knockdown via small interfering RNA reversed the effects of DEPDC1 overexpression in HCC cells. Furthermore, it was revealed that conditioned medium from DEPDC1 upregulated Li-7 and Hep3B cells led to angiogenesis in vitro, whereas CCL20 knockdown in Li-7 and Hep3B cells or CCR6 knockdown in human umbilical vein endothelial cells reversed the angiogenic effect of DEPDC1 overexpression. In conclusion, DEPDC1 facilitated cell proliferation, invasion and angiogenesis via the CCL20/CCR6 pathway in HCC.

• Animals
• Apoptosis
• Cells, Cultured
• Chemokine CCL4/genetics
• Chemokine CCL4/metabolism
• Chondrocytes/metabolism
• Collagen/metabolism
• Male
• Mice
• MicroRNAs/genetics
• MicroRNAs/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Osteoarthritis/metabolism

Despite recent advances, breast cancer (BrCa) still affects many women and the impact is disproportional in African Americans (AA) compared to European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting contribution of biological differences in BrCa disparity. Our laboratory was first to show involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner and KMplotter, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, -7, -11, -17, -20, -22 and -25 in BrCa tissues. High mRNA levels of CCL7, -8, -17, -20 and -25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, -7, -8, -17, -20 and -25 was highest in TNBC. Expression of CCL11 and CCL22 was associated with HER2. CCL7, -8, -17, -20 and -25 were elevated in AAs. In conclusion, our analysis suggests significant association of CC-chemokines in BrCa progression, OS and disparate disease outcome in AA compared to EA patients.

We have demonstrated the cytotoxic effects of [Pt(O,O′-acac)(γ-acac)(dimethyl sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in murine xenograft models in vivo. Recently, we also showed that [Pt(O,O′-acac)(γ-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and in vitro. In the present paper, apoptotic and autophagic effects of [Pt(O,O′-acac)(γ-acac)(DMS)] and cisplatin were studied and compared using Caki-1 cancerous renal cells. The effects of cisplatin include activation of caspases, proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not induce caspase activation, nor chromatin condensation or DNA fragmentation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] include microtubule-associated proteins 1A/1B light chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. [Pt(O,O′-acac)(γ-acac)(DMS)] also modulated various kinases involved in intracellular transduction regulating cell fate. [Pt(O,O′-acac)(γ-acac)(DMS)] inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a kinase activity pattern consistent with autophagy induction. In conclusion, while in past reports the high cytotoxicity of [Pt(O,O′-acac)(γ-acac)(DMS)] was always attributed to its ability to trigger an apoptotic process, in this paper we show that Caki-1 cells die as a result of the induction of a strong autophagic process.

• apoptosis
• autophagy
• cancerous renal cells
• cisplatin

• Antineoplastic Agents/chemical synthesis
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Autophagy/drug effects
• Carcinoma, Renal Cell/drug therapy
• Carcinoma, Renal Cell/pathology
• Cell Cycle/drug effects
• Cell Proliferation/drug effects
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Organoplatinum Compounds/chemical synthesis
• Organoplatinum Compounds/chemistry
• Organoplatinum Compounds/pharmacology
• Structure-Activity Relationship
• Tumor Cells, Cultured

• TGF β signaling
• endometrial cancer
• female reproduction
• knockout mouse
• uterine hyperplasia

• Animals
• Carcinogenesis/genetics
• Cell Proliferation/genetics
• Endometrium/metabolism
• Endometrium/pathology
• Female
• Gene Expression Regulation/genetics
• Humans
• Infertility/genetics
• Infertility/pathology
• Mice
• Mice, Knockout
• Pregnancy
• Receptors, Progesterone/genetics
• Smad2 Protein/genetics
• Smad3 Protein/genetics
• Uterine Neoplasms/genetics
• Uterine Neoplasms/pathology
• Uterus/metabolism
• Uterus/pathology

• K12 GM084897 NIGMS NIH HHS
• R01 HD033438 NICHD NIH HHS
• P30 CA125123 NCI NIH HHS
• R01 HD032067 NICHD NIH HHS
• L50 HD085320 NICHD NIH HHS
• K99 HD096057 NICHD NIH HHS

• Breast cancer
• CCL20
• CXCL14
• CXCR7
• HMGA2
• Notch signalling
• SEMA3C
• metastasis

Prototypical functions of the chemokine receptor CCR6 include immune regulation by maneuvering cell chemotaxis and selective delimiting of the pro-inflammatory T_H17 and regulatory T_reg subsets during chronic or acute systemic inflammation. Inhibition of CCR6 is proposed to attenuate disease symptoms and promote recuperation of multiple inflammatory and autoimmune disorders. Prescription medicines with pharmacodynamics involving the inhibition of the chemokine axis CCR6–CCL20 are very limited. The development of such therapeutics is still at an early experimental stage and has mostly involved the utilization of pre-clinical models and neutralizing mono or polyclonal antibodies against either partner (CCR6 or CCL20). Other methods include the constitutive use of small molecules as peptide inhibitors or small interfering ribonucleic acid (siRNA) to interfere with transcription at the nuclear level. In our review, we aim to introduce the wide array of potential CCR6–CCL20 inhibitors with an emphasis on attendant immune-modulator capacity that have been tested in the research field to date and are immensely promising compounds as forerunners of future curatives. Sixteen different tractable inhibitors of the CCR6–CCL20 duo have been identified as possessing high medicinal potential by drug developers worldwide to treat autoimmune and inflammatory diseases as shown in Figure 1. A multitude of antibody preparations are already available in the current pharmaceutical market as patented treatments for diseases in which the CCR6–CCL20 axis is operative, yet they must be used only as supplements with existing routinely prescribed medication as they collectively produce adverse side effects. Novel inhibitors are needed to evaluate this invaluable therapeutic target which holds much promise in the research and development of complaisant remedies for inflammatory diseases.

• CCL20
• CCR6
• TH17
• Treg
• cancer
• inflammatory diseases
• inhibitors

• Antibodies/therapeutic use
• Autoimmune Diseases/drug therapy
• Autoimmune Diseases/immunology
• Chemokine CCL20/antagonists & inhibitors
• Chemokine CCL20/immunology
• Drug Discovery
• Humans
• Immunomodulation
• Inflammation/drug therapy
• Inflammation/immunology
• Molecular Mimicry/immunology
• Molecular Targeted Therapy
• Neoplasms/drug therapy
• Neoplasms/immunology
• Receptors, Artificial/therapeutic use
• Receptors, CCR6/antagonists & inhibitors
• Receptors, CCR6/immunology
• T-Lymphocytes, Regulatory/immunology
• Th17 Cells/immunology

To develop a novel hepatocyte serum-free medium based on sericin, and to explore the effect of sericin on the hepatocyte transcriptome.

A controlled trial comparing novel serum-free medium and other media: C3A cells were cultured in our novel serum-free medium, HepatoZYME, complete medium (DMEM/F12 with 100 mL/L FBS), and DMEM/F12, and then cell attachment, proliferation, and function as well as the biocompatibility of the media were assessed. A comparative study of serum-free media with or without 2 mg/mL sericin: the effect of sericin on C3A growth was assessed by cell viability and proliferation, the effect of sericin on C3A cell cycle distribution was determined by flow cytometry, and the effect of sericin on the C3A transcriptome was assessed by gene-chip array and RT-qPCR.

More C3A cells attached to the plate containing our serum-free medium than to those containing HepatoZYME and DMEM/F12 at 24 h post-seeding. Both the viability and proliferation rate of C3A cells in sericin-based serum-free medium were superior to those of cells in HepatoZYME and DMEM/F12 (P < 0.001). The content of albumin and urea in our serum-free medium was significantly higher than that in HepatoZYME and DMEM/F12 throughout the whole culture period (P < 0.001) and was similar to that in complete medium at day 3, 4, and 5. In part 2, cell viability and proliferation were greater in the presence of 2 mg/mL sericin (P < 0.001), as was the proportion of cells in S phase (16.21% ± 0.98% vs 12.61% ± 0.90%, P < 0.01). Gene-chip array analysis indicated that the expression of CCR6, EGFR, and FOS were up-regulated by 2 mg/mL sericin, and RT-qPCR revealed that the expression of CCR6, EGFR, FOS, AKT1, JNK1, NFkB1, MMP-9, MEK2, ERK1/2 and MYC was up-regulated by 2 mg/mL sericin (P < 0.05).

We developed a novel hepatocyte serum-free medium. Sericin probably enhances cell attachment through the CCR6-Akt-JNK-NF-κB pathway and promotes cell proliferation through CCR6-mediated activation of the ERK1/2-MAPK pathway.

• Sericin
• Serum-free medium
• MAPK pathway
• Bioartificial liver support system
• CCR6

• Cell Adhesion/drug effects
• Cell Culture Techniques/methods
• Cell Division/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Culture Media, Serum-Free/chemistry
• Culture Media, Serum-Free/pharmacology
• Gene Expression Profiling/methods
• Hepatocytes/drug effects
• Hepatocytes/metabolism
• Humans
• Oligonucleotide Array Sequence Analysis/methods
• Sericins/pharmacology
• Transcriptome/drug effects

• ADP
• Akt
• ERK1/2
• MMP
• NF-κB
• P2Y1
• human mesothelioma cells

RANK/RANKL facilitates migration/invasion via epithelial-mesenchymal transition (EMT) in certain malignant tumors. The relationship and mechanism between RANK/RANKL and EMT in endometrial cancer (EC) cells, however, remain unclear. In this study, we firstly showed that RANK/RANKL activation was correlated with EC staging and EMT markers in human EC tissue specimen. RANK/RANKL promoted migration/invasion and initiated EMT of EC cell lines. Then, protein chip analysis and enzyme-linked immunosorbent assay (ELISA) revealed that the expression and secretion of chemokine ligand 20 (CCL20) was dramatically enhanced in RANKL-treated RANK over-expressed EC cells. Moreover, the higher level of CCL20 in both serum and tumor tissue was detected in orthotopic transplantation mouse models. Finally, we confirmed that CCL20 contributed to invasion and EMT of RANK over-expressed EC cells. In summary, all data supported the hypothesis that RANK/RANKL elevated the expression and secretion of CCL20 in EC cells, which promoted cancer progression through EMT.

• CCL20
• RANK
• RANKL
• endometrial cancer
• epithelial-mesenchymal transition

Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia-inducible factor-dependent signaling. In this study, we investigated the effects of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to identify potential genes and microRNAs associated with tumor malignancy. The transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term hypoxia were analyzed using next-generation sequencing. The results showed that long-term hypoxia promoted the ability of colony formation and transwell migration compared to normoxia. In addition, the differentially expressed genes induced by long-term hypoxia were involved in various biological processes including cell proliferation, the tumor necrosis factor signaling pathway, basal cell carcinoma and cancer pathways. The upregulated (L1CAM and FBN1) and downregulated (AUTS2, MAPT, AGT and USH1C) genes in 786-O under long-term hypoxia were also observed in clinical ccRCC samples along with malignant grade. The expressions of these genes were significantly correlated with survival outcomes in patients with renal cancer. We also found that long-term hypoxia in 786-O resulted in decreased expressions of hsa-mir-100 and hsa-mir-378 and this effect was also observed in samples of metastatic ccRCC compared to samples of non-metastatic ccRCC. These findings may provide a new direction for the study of potential molecular mechanisms associated with the progression of ccRCC.

• clear cell renal cell carcinoma
• long-term hypoxia
• next-generation sequencing
• poor survival

• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Angiotensinogen/genetics
• Angiotensinogen/metabolism
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/metabolism
• Cell Cycle Proteins
• Cell Hypoxia
• Cell Line, Tumor
• Cytoskeletal Proteins
• Fibrillin-1/genetics
• Fibrillin-1/metabolism
• Humans
• Kidney Neoplasms/genetics
• Kidney Neoplasms/metabolism
• MicroRNAs/genetics
• Neural Cell Adhesion Molecule L1/genetics
• Neural Cell Adhesion Molecule L1/metabolism
• Oxygen/metabolism
• Proteins/genetics
• Proteins/metabolism
• Transcription Factors
• Transcriptome
• tau Proteins/genetics
• tau Proteins/metabolism

• R01 DK107009 NIDDK NIH HHS

• Adipose-derived mesenchymal stem cells
• Conditioned medium
• Gastric mucosal injury
• Hypoxia
• Secretome

• ADP
• P2Y1
• PKC-α
• PKC-δ
• human mesothelioma cells
• p53

• JAK
• MAPK
• NF-kB
• PKC
• STAT

• Animals
• Cells, Cultured
• DNA/metabolism
• Gene Expression Regulation
• HeLa Cells
• Humans
• Mice, Inbred C57BL
• NF-kappa B/metabolism
• Nuclear Proteins/metabolism
• Nuclear Proteins/physiology
• Nucleophosmin
• Protein Binding
• Transcription Factor RelA/metabolism
• Transcription, Genetic

We investigated the role of the transcriptional mediator subunit 23 (MED23) in everolimus drug resistance, invasion and metastasis during breast cancer treatment and its molecular mechanism. We also evaluated the endocrinotherapy and prevention method for breast cancer. Breast cancer cell strains were established that can continuously express MED23, as well as inducible MED23-shRNA expression plasmids. The inductive agent, doxycycline (Dox), was added to the water for long-term silencing of MED23 in intratumoral cells. We conducted experiments on the role of MED23 in the regulation of invasion and metastasis of breast cancer using cell culture, western blotting, MTT proliferation experiment, fluorescent quantitative PCR and chromatin immunoprecipitation (ChIP). The silencing of MED23 significantly inhibited cellular growth and proliferation as well as soft agar cloning. Silencing of MED23 strengthened the sensitivity of the everolimus-resistant breast cancer cell strains BT474 and MCF-7/ADM cells to everolimus medication. The silencing of MED23, in combination with everolimus, inhibits the cell cycle progress of breast cancer cells. ChIP indicated that the mutual regulation of HER2 and MED23 also participates in the formation of the everolimus drug resistance mechanism. Therefore, MED23 plays an important role in everolimus drug resistance, invasion, and metastasis of breast cancer. As a potential molecular therapeutic target of breast cancer, MED23 overcomes drug resistance in clinical endocrinotherapy and controls the distal relapse and metastasis in breast cancer by the targeted silencing of MED23.

• MED23
• breast cancer
• everolimus
• invasion
• metastasis

• Phospholipase Cε
• Scar formation
• Wound healing

• Angiogenesis
• Antitumor immune response
• Apoptosis
• Cancer stem cells
• Chemokines
• Proliferation
• Receptor
• Senescence

• NF-kB transcription factor
• breast cancer
• cell migration
• cell signaling
• inflammation
• macrophage

• BONE MODELING AND REMODELING
• CELL/TISSUE SIGNALING
• CYTOKINES
• OSTEOBLAST

We have previously shown that overexpression of BLyS/BAFF was associated with increased relative frequencies of innate “precursor” marginal zone (MZ)-like B-cells in the blood of HIV-1-infected rapid and classic progressors. However, along with relatively normal BLyS/BAFF expression levels, these cells remain unaltered in elite-controllers (EC), rather, percentages of more mature MZ-like B-cells are decreased in the blood of these individuals. Fluctuations in frequencies of blood MZ-like B-cell populations may reflect migratory patterns associated with disease progression status, suggesting an important role for these cells in HIV-1 pathogenesis. We have therefore longitudinally measured plasma levels of B-tropic chemokines by ELISA-based technology as well as their ligands by flow-cytometry on blood B-cell populations of HIV-1-infected individuals with different rates of disease progression and uninfected controls. Migration potential of B-cell populations from these individuals were determined by chemotaxis assays. We found important modulations of CXCL13-CXCR5, CXCL12-CXCR4/CXCR7, CCL20-CCR6 and CCL25-CCR9 chemokine-axes and increased cell migration patterns in HIV progressors. Interestingly, frequencies of CCR6 expressing cells were significantly elevated within the precursor MZ-like population, consistent with increased migration in response to CCL20. Although we found little modulation of chemokine-axes in EC, cell migration was greater than that observed for uninfected controls, especially for MZ-like B-cells. Overall the immune response against HIV-1 may involve recruitment of MZ-like B-cells to peripheral sites. Moreover, our findings suggest that “regulated” attraction of these cells in a preserved BLyS/BAFF non-inflammatory environment, such as encountered in EC could be beneficial to the battle and even control of HIV.

• CCL20
• PI3K
• cancer
• epithelium
• lung
• production

• A549 Cells
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Chemokine CCL20/agonists
• Chemokine CCL20/genetics
• Chemokine CCL20/metabolism
• Flavonoids/pharmacology
• Gene Expression Regulation, Neoplastic
• Humans
• Imidazoles/pharmacology
• Interleukin-1beta/pharmacology
• Mitogen-Activated Protein Kinase 1/genetics
• Mitogen-Activated Protein Kinase 1/metabolism
• Mitogen-Activated Protein Kinase 3/genetics
• Mitogen-Activated Protein Kinase 3/metabolism
• Phosphatidylinositol 3-Kinases/genetics
• Phosphatidylinositol 3-Kinases/metabolism
• Protein Kinase Inhibitors/pharmacology
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Pyridines/pharmacology
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases/genetics
• p38 Mitogen-Activated Protein Kinases/metabolism