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

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. 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. 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. these results suggest that ARHGAP17 might serve as a tumor suppressor in colon cancer progression and metastasis through Wnt/β-catenin signaling pathway.

Pan S ，Deng Y ，Fu J ，Zhang Y ，Zhang Z ，Ru X ，Qin X ... -  《-》

Tumor suppressor DLC-1 induces apoptosis and inhibits the growth and invasion of colon cancer cells through the Wnt/β-catenin signaling pathway.

Wang C ，Wang J ，Liu H ，Fu Z ... -  《-》

ARHGAP17 suppresses tumor progression and up-regulates P21 and P27 expression via inhibiting PI3K/AKT signaling pathway in cervical cancer.

ARHGAP17 has long been thought to be involved in the maintenance of tight junction and epithelial barrier. Recently, a few Rho GTPase activating proteins (RhoGAPs) have been identified as tumor suppressors in some human cancers. The present study aimed to explore ARHGAP17 expression in cervical cancer and the possible function in tumor progression. ARHGAP17 expression in cervical cancer cell lines was assessed by RT-PCR and Western blotting. ARHGAP17 expression in cervical cancer tissues and normal tissues was assessed by immunohistochemistry. The cell proliferation was determined using CCK-8 in vitro and subcutaneous xenograft model in vivo. Here, we showed lower expression of ARHGAP17 in cell lines and human cervical cancer samples. Manipulation of ARHGAP17 affected cell proliferation in vitro and tumor growth in vivo. Furthermore, the phosphorylation of AKT was enhanced in ARHGAP17 silencing cervical cancer cells. ARHGAP17 can elevate P21 and P27 expression level through inhibiting PI3K/AKT signaling pathway. Stepwise investigations demonstrated that ARHGAP17 suppressed malignant phenotype of cervical cancer cells via inhibiting PI3K/AKT signaling pathway. These results reveal that ARHGAP17 functions as a tumor suppressor in cervical cancer that suppresses tumor growth, at least partly, through inhibition of PI3K/AKT signaling and up-regulation of P21 and P27 expression.

Guo Q ，Xiong Y ，Song Y ，Hua K ，Gao S ... -  《-》

Increased Expression of the YPEL3 Gene in Human Colonic Adenocarcinoma Tissue and the Effects on Proliferation, Migration, and Invasion of Colonic Adenocarcinoma Cells In Vitro via the Wnt/b-Catenin Signaling Pathway.

Kong X ，Li Y ，Zhang X 《-》

MicroRNA-27a Promotes the Proliferation and Invasiveness of Colon Cancer Cells by Targeting SFRP1 through the Wnt/β-Catenin Signaling Pathway.

This study aims to explore the effects of microRNA-27a (miR-27a) on the proliferation and invasiveness of colon cancer cells through the Secreted Frizzled-related protein 1 (SFRP1) and the Wnt/β-catenin signaling pathway. Colon cancer tissues and adjacent normal tissues from 125 colon cancer patients, together with the HCEpic, HCT-116, HT-29, SW480 and SW620 cell lines, were prepared for this study. The transfected HCT-116 cells were divided into the miR-27a mimics, miR-27a-NC, anti-miR-27a, blank, Lv-SFRP1, Lv-NC, and miR-27a mimics + Lv-SFRP1 groups. RT-qPCR was performed to detect the expressions of miR-27a and SFRP1 mRNA. A dual-luciferase reporter assay was conducted to examine the effect of miR-27a on SFRP1. Western blotting was used to measure the expressions of the SFRP1, β-catenin, GSK-3β, p-β-catenin, p-GSK-3β, c-Myc and cyclin D1 proteins. MTT, soft agar clone formation and Transwell chamber assays were performed to detect cell proliferation and invasion. Compared with normal tissues and cells, colon cancer tissues and cells demonstrated significantly higher expression of miR-27a, but lower expressions of SFRP1 mRNA and protein. MiR-27a negatively regulated the expression of SFRP1 mRNA. SFRP1 was also found to be a target gene of miR-27a. In the miR-27a mimic group, the proliferation and invasiveness of colon cancer cells were significantly increased, while the expressions of GSK-3 β and p-β-catenin were remarkably down-regulated; in contrast, the expressions of p-GSK-3β, -catenin, c-Myc and cyclin D1 were up-regulated. While the proliferation and invasiveness of colon cancer cells in the anti-miR-27a and Lv-SFRP1 groups were decreased, the expressions of GSK-3β and p-β-catenin were elevated, and the expressions of p-GSK-3β, β-catenin, c-Myc and cyclin D1 were decreased. These findings indicated that miR-27a could promote the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/β-catenin signaling pathway.

Ba S ，Xuan Y ，Long ZW ，Chen HY ，Zheng SS ... -  《-》