Role of caveolin‐1 in hepatocellular carcinoma arising from non‐alcoholic fatty liver disease. Issue 8 (7th July 2018)

• Record Type: Journal Article
• Authors: Takeda, Makoto; Sakaguchi, Takanori; Hiraide, Takanori; Shibasaki, Yasushi; Morita, Yoshifumi; Kikuchi, Hirotoshi; Ikegami, Koji; Setou, Mitsutoshi; Konno, Hiroyuki; Takeuchi, Hiroya
• Is Part Of: Cancer science. Volume 109:Issue 8(2018)
• Page Start: 2401
• Page End: 2411
• Publication Date: 2018-07-07
• Subjects: apoptosis -- caveolin‐1 -- ceramide -- hepatocellular carcinoma -- non‐alcoholic fatty liver disease; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13659
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Hepatocellular carcinoma (HCC) associated with non‐alcoholic fatty liver disease (NAFLD) and hepatitis C virus infection has distinct gene expression profiles. Caveolin (CAV)‐1 was upregulated in clinical samples of NAFLD‐HCC, and CAV‐1 overexpression was linked to increased proliferation in HCC cell lines. CAV‐1 prevents HCC cell apoptosis under oleic acid‐rich conditions such as NAFLD.