YMO1 suppresses invasion and metastasis by inhibiting RhoC signaling and predicts favorable prognosis in hepatocellular carcinoma
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Rui-Min Chang1, Lei Pei1, Feng Fang1, Jiang-Feng Xu1, Hao Yang1, Chao-Hui Zuo4, Jian-Hua Zhou2, Geng-Qiu Luo2, Lian-Yue Yang1,3
1Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, China
2Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China
3Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
4Department of Abdominal Surgical Oncology, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
Lian-Yue Yang, email: [email protected]
Keywords: YMO1, RhoC, PAX5, hepatocellular carcinoma, metastasis
Received: November 21, 2015 Accepted: June 29, 2016 Published: July 27, 2016
Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro. In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity.
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