|
|
|
| CADM1 regulates the G1/S transition and represses tumorigenicity through the Rb-E2F pathway in hepatocellular carcinoma |
| Wu Zhang, Hai-Yang Xie, Song-Ming Ding, Chun-Yang Xing, An Chen, Ming-Chun Lai, Lin Zhou and Shu-Sen Zheng |
Hangzhou, China
Author Affiliations: Department of Hepatobiliary and Pancreatic Surgery, Shulan Hospital, Hangzhou 310000, China (Zhang W); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang University School of Medicine, Hangzhou 310003, China (Zhang W, Xie HY, Zhou L and Zheng SS); Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Zhang W, Ding SM, Xing CY, Chen A, Lai MC and Zheng SS)
Corresponding Author: Prof. Shu-Sen Zheng, MD, PhD, FACS, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, and Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel: +86-571-87236570; Fax: +86-571-87236628; Email: shusenzheng@zju.edu.cn) |
|
|
|
|
Abstract BACKGROUND: Increasing evidence indicates that downregulation of cell adhesion molecule 1 (CADM1) contributes to tumorigenesis in various cancers. The present study was undertaken to investigate the CADM1 expression pattern in human hepatocellular carcinoma (HCC), and to elucidate the mechanism underlying CADM1-mediated tumor suppression.
METHODS: CADM1 expression in HCC cell lines was measured by quantitative real-time PCR. The function of CADM1 in the context of tumor suppression in HCC cells was determined using proliferation assays, cell cycle analysis, EdU incorporation assays, in vitro colony formation analysis, and in vivo tumorigenicity assays. The mechanism by which CADM1 acts as a tumor suppressor gene in HCC was investigated using Western blotting analysis.
RESULTS: Downregulation of CADM1 expression is frequently detected in both HCC cells and clinical samples. Restoration of CADM1 expression in HCC cell lines significantly inhibits cell growth and negatively regulates the G1/S transition. CADM1 overexpression can inhibit the tumorigenicity of HCC cells both in vitro and in vivo. Western blotting analysis revealed that ectopic expression of CADM1 in HCC cells is associated with increased expression of Retinoblastoma (Rb) protein.
CONCLUSIONS: Our results showed that suppression of tumorigenesis by CADM1 may be mediated by the Rb-E2F pathway, involving upregulation of Rb protein levels. This pathway could therefore represent an attractive target for HCC therapy.
|
|
|
|
|
|
|
|
|
2016, Vol. 15 
