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Role of caveolin-1 in hepatocellular carcinoma arising from non-alcoholic fatty liver disease.


ABSTRACT: The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1. HLE cells treated with oleic acid (OA) showed robust proliferation, whereas CAV-null HepG2 cells showed reduced proliferation and increased apoptosis. CAV-1 knockdown in HLE cells attenuated the OA-induced increase in proliferation and enhanced apoptosis. Liquid chromatography-tandem mass spectrometry analysis revealed that the levels of OA-containing ceramide, a pro-apoptotic factor, were higher in HepG2 and CAV-1-deficient HLE cells than in HLE cells, suggesting that CAV-1 inhibits apoptosis by decreasing the level of OA-containing ceramide. These results indicate that CAV-1 is important for NAFLD-HCC survival in fatty acid-rich environments and is a potential therapeutic target.

SUBMITTER: Takeda M 

PROVIDER: S-EPMC6113505 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Role of caveolin-1 in hepatocellular carcinoma arising from non-alcoholic fatty liver disease.

Takeda Makoto M   Sakaguchi Takanori T   Hiraide Takanori T   Shibasaki Yasushi Y   Morita Yoshifumi Y   Kikuchi Hirotoshi H   Ikegami Koji K   Setou Mitsutoshi M   Konno Hiroyuki H   Takeuchi Hiroya H  

Cancer science 20180707 8


The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expre  ...[more]

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