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 ... -  《-》

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 ... -  《-》

Slug inhibits the proliferation and tumor formation of human cervical cancer cells by up-regulating the p21/p27 proteins and down-regulating the activity of the Wnt/β-catenin signaling pathway via the trans-suppression Akt1/p-Akt1 expression.

Cui N ，Yang WT ，Zheng PS 《Oncotarget》

PI3K/AKT pathway-mediated regulation of p27(Kip1) is associated with cell cycle arrest and apoptosis in cervical cancer.

Prasad SB ，Yadav SS ，Das M ，Modi A ，Kumari S ，Pandey LK ，Singh S ，Pradhan S ，Narayan G ... -  《-》

Msi1 promotes tumor growth and cell proliferation by targeting cell cycle checkpoint proteins p21, p27 and p53 in cervical carcinomas.

Liu X ，Yang WT ，Zheng PS 《Oncotarget》