Wei-Ren Liu1, Lei Jin1, Meng-Xin Tian1, Xi-Fei Jiang1, Liu-Xiao Yang1, Zhen-Bin Ding1, Ying-Hao Shen1, Yuan-Fei Peng1, Dong-Mei Gao1, Jian Zhou2, Shuang-Jian Qiu1, Zhi Dai1, Jia Fan2, Ying-Hong Shi3. 1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180, FengLin Road, 200032 Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China. 2. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180, FengLin Road, 200032 Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China. 3. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180, FengLin Road, 200032 Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China. Electronic address: shi.yinghong@zs-hospital.sh.cn.
Abstract
BACKGROUND: Caveolin-1 is a member of the caveolae family of membrane proteins. Although some researchers have investigated the function of Caveolin-1 in hepatocellular carcinoma, the mechanism of Caveolin-1 action and its prognostic value in hepatocellular carcinoma remain unclear. METHODS: Caveolin-1 expression was measured in hepatocellular carcinoma cell lines and tissues using quantitative reverse transcription-polymerase chain reaction, western blot, and immunofluorescence assays. In in vitro experiments, Caveolin-1 was depleted using a short hairpin RNA lentiviral vector, and tumor cell behavior was analyzed. The effect of Caveolin-1 on hepatocellular carcinoma cell autophagy was investigated. Prognostic value of Caveolin-1 was analyzed by immunohistochemistry in two cohorts that included a total of 721 hepatocellular carcinoma patients. RESULTS: We found that Caveolin-1 was overexpressed in highly metastatic hepatocellular carcinoma cell lines and tumor tissues. Moreover, Caveolin-1 promoted hepatocellular carcinoma cell proliferation, migration, and angiogenesis and inhibited autophagy. Finally, Caveolin-1 expression in hepatocellular carcinoma tissues was inversely correlated with patient overall survival and time to recurrence. CONCLUSION: Our data obtained from cell lines suggest an oncogenic role for Caveolin-1 in hepatocellular carcinoma, Caveolin-1 contributed to hepatocellular carcinoma cell autophagy deficiency. Furthermore, Caveolin-1 may function as a novel prognostic indicator for hepatocellular carcinoma patients after curative resection, and combination of targeted therapy aimed at Caveolin-1 and autophagy modulation may represent an effective way to treat hepatocellular carcinoma.
BACKGROUND:Caveolin-1 is a member of the caveolae family of membrane proteins. Although some researchers have investigated the function of Caveolin-1 in hepatocellular carcinoma, the mechanism of Caveolin-1 action and its prognostic value in hepatocellular carcinoma remain unclear. METHODS:Caveolin-1 expression was measured in hepatocellular carcinoma cell lines and tissues using quantitative reverse transcription-polymerase chain reaction, western blot, and immunofluorescence assays. In in vitro experiments, Caveolin-1 was depleted using a short hairpin RNA lentiviral vector, and tumor cell behavior was analyzed. The effect of Caveolin-1 on hepatocellular carcinoma cell autophagy was investigated. Prognostic value of Caveolin-1 was analyzed by immunohistochemistry in two cohorts that included a total of 721 hepatocellular carcinomapatients. RESULTS: We found that Caveolin-1 was overexpressed in highly metastatic hepatocellular carcinoma cell lines and tumor tissues. Moreover, Caveolin-1 promoted hepatocellular carcinoma cell proliferation, migration, and angiogenesis and inhibited autophagy. Finally, Caveolin-1 expression in hepatocellular carcinoma tissues was inversely correlated with patient overall survival and time to recurrence. CONCLUSION: Our data obtained from cell lines suggest an oncogenic role for Caveolin-1 in hepatocellular carcinoma, Caveolin-1 contributed to hepatocellular carcinoma cell autophagy deficiency. Furthermore, Caveolin-1 may function as a novel prognostic indicator for hepatocellular carcinomapatients after curative resection, and combination of targeted therapy aimed at Caveolin-1 and autophagy modulation may represent an effective way to treat hepatocellular carcinoma.