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

Clin Res Hepatol Gastroenterol. 2016 Apr;40(2):169-78. doi: 10.1016/j.clinre.2015.06.017. Epub 2015 Jul 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / secondary*
  • Caveolin 1 / biosynthesis
  • Caveolin 1 / physiology*
  • Cell Proliferation
  • Female
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Tumor Cells, Cultured

Substances

  • CAV1 protein, human
  • Caveolin 1