ARHGEF7 promotes metastasis of colorectal adenocarcinoma by regulating the motility of cancer cells

Lei,Xiong; Deng,Li; Liu,Dongning; Liao,Shijun; Dai,Hua; Li,Jiaxi; Rong,Jun; Wang,Zhiwen; Huang,Guodong; Tang,Cheng; Xu,Chen; Xiao,Benping; Li,Taiyuan

doi:10.3892/ijo.2018.4535

ARHGEF7 promotes metastasis of colorectal adenocarcinoma by regulating the motility of cancer cells

Authors:
- Xiong Lei
- Li Deng
- Dongning Liu
- Shijun Liao
- Hua Dai
- Jiaxi Li
- Jun Rong
- Zhiwen Wang
- Guodong Huang
- Cheng Tang
- Chen Xu
- Benping Xiao
- Taiyuan Li
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of General Surgery, Jiangxi Pingxiang People's Hospital, Pingxiang, Jiangxi 337000, P.R. China, Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: August 22, 2018 https://doi.org/10.3892/ijo.2018.4535
Pages: 1980-1996
Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have shown that Rho guanine nucleotide exchange factor 7 (ARHGEF7) is implicated in cytoskeleton remodelling, which is important for cell motility and invasiveness, and exhibits frequent high-level genetic amplification in metastatic lesions of colorectal adenocarcinoma. Therefore, it was hypothesized that ARHGEF7 may be involved in the metastasis of colorectal adenocarcinoma. In the present study, it was demonstrated that the expression level of ARHGEF7 was significantly upregulated in colorectal adenocarcinoma tumor tissues compared with matched nontumorous tissues, and its expression level correlated with colorectal adenocarcinoma metastasis. In vitro assays showed that the overexpression of ARHGEF7 in CRC cells significantly enhanced cell migration and invasion, whereas the knockdown of ARHGEF7 in colorectal adenocarcinoma cells significantly decreased cell migration and invasion. In vivo assays showed that the overexpression of ARHGEF7 in CRC cells facilitated tumor metastasis, whereas the knockdown of ARHGEF7 in CRC cells significantly inhibited tumor metastasis. Furthermore, it was demonstrated that ARHGEF7 promoted cell motility by regulating the actin cytoskeleton. Finally, according to ReMARK guidelines for reporting prognostic biomarkers in cancer, it was found that a high expression of ARHGEF7 was significantly correlated with lymph node, mesenteric and distant metastasis. Patients with colorectal adenocarcinoma with a high expression of ARHGEF7 had shorter disease-free survival (DFS) and shorter overall survival (OS) rates, compared with those with a low expression of ARHGEF7, as determined by the Kaplan-Meier method with a log-rank test. Cox regression analysis showed that a high expression of ARHGEF7 was an independent risk factor for DFS and OS rates in colorectal adenocarcinoma.

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