Caveolin-1 promotes tumor growth and metastasis via autophagy inhibition in hepatocellular carcinoma

• Published in: Clinics and research in hepatology and gastroenterology Vol. 40; no. 2; pp. 169 - 178
• Main Authors: Liu, Wei-Ren, Jin, Lei, Tian, Meng-Xin, Jiang, Xi-Fei, Yang, Liu-Xiao, Ding, Zhen-Bin, Shen, Ying-Hao, Peng, Yuan-Fei, Gao, Dong-Mei, Zhou, Jian, Qiu, Shuang-Jian, Dai, Zhi, Fan, Jia, Shi, Ying-Hong
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.04.2016
• Subjects: Autophagy - physiology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - secondary; Caveolin 1 - biosynthesis; Caveolin 1 - physiology; Cell Proliferation; Female; Gastroenterology and Hepatology; Humans; Internal Medicine; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Middle Aged; Prognosis; Tumor Cells, Cultured; Cav-1; TNM; TTR; OS; CI; qRT-PCR; γ-GT; HCC; TMA; HR; AFP; EMT; Caveolin-1; Quantitative reverse transcription-polymerase chain reaction; Confidential interval; Hepatocellular carcinoma; Time to recurrence; Tissue microarray; Hazard ratio; Epithelial-to-mesenchymal transition; γ-glutamyl transferase; α-fetoprotein; Overall survival; Tumor-nodes-metastasis
• ISSN: 2210-7401; 2210-741X; 2210-741X
• DOI: 10.1016/j.clinre.2015.06.017

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. 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. 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. 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.