scholarly journals Tumor Suppressive Role of ARHGAP17 in Colon Cancer Through Wnt/β-Catenin Signaling

2018 ◽  
Vol 46 (5) ◽  
pp. 2138-2148 ◽  
Author(s):  
Shengli Pan ◽  
Yingying Deng ◽  
Jun Fu ◽  
Yuhao Zhang ◽  
Zhijin Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Rho Gtpase ◽  
Gene Set Enrichment Analysis ◽  
Cell Counting ◽  
Normal Colonic Mucosa ◽  
Colon Cancer Cells

Background/Aims: A few Rho GTPase activating proteins (RhoGAPs) have been identified as tumor suppressors in a variety of human cancers. ARHGAP17, a member of RhoGAPs, has been reported to be involved in the maintenance of tight junction and epithelial barrier. The present study aimed to explore its expression in colon cancer and the possible function in colonic carcinogenesis. Methods: The mRNA and protein expression was assessed by realtime PCR and immunoblotting, respectively. Cell Counting Kit-8 (CCK-8) and Transwell assays were performed to evaluate cell proliferation and invasion, respectively. Results: We found that ARHGAP17 expression was obviously lower in colon cancer specimens than in normal colonic mucosa. ARHGAP17 expression was associated with tumor stage, size and differentiation. In vitro analysis demonstrated that ARHGAP17 overexpression inhibited cell growth and invasion of HCT-8 and HCT-116 cells. In addition, an in vivo experimental metastasis model showed that ARHGAP17 overexpression restricted cancer metastasis to the lung. Mechanically, we found that Wnt signaling contributed to the functions of ARHGAP17 in colon cancer cells. Gene set enrichment analysis (GSEA) in The Cancer Genome Atlas dataset showed that the Wnt signaling pathway was negatively associated with ARHGAP17 expression. The mRNA expression of β-catenin (an important signaling transducer of canonical Wnt signaling) gene (CTNNB1) was negatively correlated with ARHGAP17 expression. Immunoblot analysis of downstream effectors of β-catenin (c-Myc/p27 and MMP7) in ARHGAP17 overexpressing colon cancer cells and metastatic tumors within the lung also validated the GSEA result. ARHGAP17 overexpression increased the phosphorylation of glycogen synthetase kinase 3β, and decreased β-catenin nuclear localization and transcriptional activity. Furthermore, inhibition of Wnt signaling by Wnt Inhibitor Factor-1 (WIF-1) in HIEC cells with ARHGAP17 knockdown significantly attenuated the promotion effects of ARHGAP17 knockdown on cell proliferation, invasion and the activation of β-catenin. Conclusion: these results suggest that ARHGAP17 might serve as a tumor suppressor in colon cancer progression and metastasis through Wnt/β-catenin signaling pathway.

scholarly journals Correlation of GOLPH3 Gene with Wnt Signaling Pathway in Human Colon Cancer Cells

2016 ◽  
Vol 7 (8) ◽  
pp. 928-934 ◽  
Author(s):  
Cheng-Zhi Qiu ◽  
Ming-Zhen Wang ◽  
Wai-Shi Yu ◽  
Yan-Ta Guo ◽  
Chun-Xiao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals Itraconazole inhibits the Hedgehog signaling pathway thereby inducing autophagy-mediated apoptosis of colon cancer cells

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Huiming Deng ◽  
Ling Huang ◽  
Zhongkai Liao ◽  
Mi Liu ◽  
Qiang Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Colon Cancer Cell ◽  
Hedgehog Signaling Pathway ◽  
Colon Cancer Cells ◽  
Hct 116

AbstractItraconazole is as an antifungal medication used to treat systemic fungal infections. Recently, it has been reported to be effective in suppressing tumor growth by inhibiting the Hedgehog signaling pathway and angiogenesis. In the present study, we investigated whether itraconazole induces autophagy-mediated cell death of colon cancer cells through the Hedgehog signaling pathway. Cell apoptosis and cell cycle distribution of the colon cancer cell lines SW-480 and HCT-116 were detected by flow cytometry and terminal TUNEL assay. Autophagy and signal proteins were detected by western blotting and cell proliferation-associated antigen Ki-67 was measured using immunohistochemistry. The images of autophagy flux and formation of autophagosomes were observed by laser scanning confocal and/or transmission electron microscopy. Colon cancer cell xenograft mouse models were also established. Itraconazole treatment inhibited cell proliferation via G1 cell cycle arrest as well as autophagy-mediated apoptosis of SW-480 and HCT-116 colon cancer cells. In addition, the Hedgehog pathway was found to be involved in activation of itraconazole-mediated autophagy. After using the Hedgehog agonist recombinant human Sonic Hedgehog (rhshh), itraconazole could counteract the activation of rhshh. Moreover, treatment with itraconazole produced significant cancer inhibition in HCT-116-bearing mice. Thus, itraconazole may be a potential and effective therapy for the treatment of colon cancer.

Celecoxib Downregulates CD133 Expression Through Inhibition of the Wnt Signaling Pathway in Colon Cancer Cells

2012 ◽  
Vol 31 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Yanhong Deng ◽  
Qiao Su ◽  
Jianwen Mo ◽  
Xinhui Fu ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Colon Cancer Cells ◽  
Cd133 Expression

scholarly journals miR-200c /FUT4 axis prevents the migration, invasion and proliferation of colon cancer cells by downregulating Wnt/β-catenin pathway

2020 ◽  
Author(s):  
Jinchun Cong ◽  
Chuanjia Yang ◽  
Zhixiu Xia ◽  
Jian Gong ◽  
Hong Zhang
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Negative Control ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Ki 67 ◽  
Sw480 Cells ◽  
Related Proteins

Abstract Background To investigate the effects of miR-200c targeting fucosyltransferase 4 (FUT4) on the proliferation, migration and invasion of colon cancer cells and further to explore its mechanism. Methods The expression of miR-200c and FUT4 mRNA in Lovo and SW480 cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and their correlation was analyzed by Pearson. LipofectamineTM 2000 transfection reagent was used to transfect miR-200c mimic, FUT4 siRNA, FUT4 mimic and FUT4 mimic negative control into Lovo and SW480 cells, and RT-PCR was used to analyze the effect of transfection. Cell counting kitcck-8 (CCK-8), cloning and transwell assays were used to detect the migration, invasion and proliferation of Lovo and SW480 cells, respectively. Immunofluorescence was used to analyze the expression of Ki-67 protein. Moreover, the expression of Wnt/β-catenin signaling pathway-related proteins were detected by western blot. Double luciferase experiment was performed to verify the targeting relationship between miR-200c and FUT4. Results Pearson results showed that miR-200c and FUT4 were negatively correlated in Lovo and SW480 cells (correlation coefficients were − 0.9046 and − 0.9236, respectively). MiR-200c overexpression inhibits the proliferation, migration and invasion of Lovo cells by down-regulating FUT4. The expression of Ki67 positive cells and Wnt/β-catenin signaling pathway-related proteins were reduced in miR-200c overexpression and FUT4 silencing groups. The scientific search and dual luciferase reporting system identified FUT4 was the target of miR-200c. Conclusion In conclusion, miR-200c overexpression inhibits FUT4 expression and down-regulates the Wnt/β-catenin signaling pathway, thereby inhibiting the migration, invasion and proliferation of colon cancer cells.

scholarly journals INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110149
Author(s):  
Jia Guo ◽  
Yuan Liu
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Counting ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Colon Cancer Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues

Objective Colon cancer has high morbidity and mortality rates, and proliferation, invasion and migration play an important role in colon cancer progression. Here, the effects of inhibin subunit beta A (INHBA) on cell proliferation, invasion and migration were investigated. Methods The UALCAN database was used to assess INHBA expression in colon cancer tissues and predict the survival of patients with high and low INHBA expression. The relevant proteins were detected by RT-qPCR and western blot. Cell transfection was performed to overexpress or inhibit INHBA and versican (VCAN). The high correlation between INHBA and VCAN found through LinkedOmics and StarBase databases was verified by immunoprecipitation assays. Cell proliferation was detected by cell counting kit-8 and colony formation assays. Wound healing and Transwell assays were used to assess migration and invasion. Results INHBA expression was upregulated in colon cancer tissues and cells. INHBA inhibition impaired the proliferation, migration and invasion of these cells. In addition, we confirmed the correlation between INHBA and VCAN in colon cancer cells. Finally, we found that INHBA interference inhibited the aggressive behavior of colon cancer cells by downregulating VCAN. Conclusion INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN.

scholarly journals Peroxiredoxin-6 regulates p38-mediated epithelial–mesenchymal transition in HCT116 colon cancer cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Unbin Chae ◽  
Bokyung Kim ◽  
HanSeop Kim ◽  
Young-Ho Park ◽  
Seung Hwan Lee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Hct116 Cell ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Hct116 Cells

Abstract Background Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial–mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators. Methods We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays. Results We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells. Conclusion We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.

scholarly journals PUM1 Is Overexpressed in Colon Cancer Cells With Acquired Resistance to Cetuximab

2021 ◽  
Vol 9 ◽  
Author(s):  
Qizhi Liu ◽  
Cheng Xin ◽  
Yikuan Chen ◽  
Jiawen Yang ◽  
Yingying Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Rna Binding ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Cell Counting ◽  
Colon Cancer Cells ◽  
Protein Levels

BackgroundCetuximab is an effective antibody to treat colorectal cancer (CRC) by targeting the epidermal growth factor receptor (EGFR). However, the mechanisms of acquired resistance to cetuximab therapy, especially in patients without identifiable gene mutations, are not fully understood.MethodsOur study investigated the role of pumilio RNA-binding family member 1 (PUM1) in cetuximab resistance. We established cetuximab-resistant colon cancer cell lines SW480R and Caco-2R and knocked out PUM1 and DEAD-box helicase 5 (DDX5) with the clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) system. To check cell proliferation, we used Cell Counting Kit-8. We performed qPCR and immunoblot to examine the levels of mRNAs and proteins for each cell line.ResultsOur data showed that PUM1 was upregulated in SW480R and Caco-2R cells with increased protein levels and cell proliferation, and PUM1 knockout reduced cell viability in the presence of cetuximab. We also found that PUM1 interacted with DDX5 in 3′ untranslated region (UTR) and positively regulated its mRNA expression. Furthermore, suppression of DDX5 also decreased the proliferation of SW480R and Caco-2R cells.ConclusionOur study suggests that PUM1 positively regulates DDX5 and acts as a promoter in cetuximab-resistant colon cancer cells.

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