Open AccessRole of caveolin‐1 in hepatocellular carcinoma arising from non‐alcoholic fatty liver disease
Author(s) -
Takeda Makoto,
Sakaguchi Takanori,
Hiraide Takanori,
Shibasaki Yasushi,
Morita Yoshifumi,
Kikuchi Hirotoshi,
Ikegami Koji,
Setou Mitsutoshi,
Konno Hiroyuki,
Takeuchi Hiroya
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13659
Subject(s) - fatty liver , hepatocellular carcinoma , apoptosis , ceramide , cancer research , oleic acid , medicine , palmitic acid , chemistry , fatty acid , endocrinology , biology , disease , biochemistry
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.