Fatty-acid-induced FABP5/HIF-1 reprograms lipid metabolism and enhances the proliferation of liver cancer cells.

ABSTRACT: Hypoxia-inducible factor-1 alpha (HIF-1?) is a transcription factor essential for cancer cell survival. The reprogramming of lipid metabolism has emerged as a hallmark of cancer, yet the relevance of HIF-1? to this process remains elusive. In this study, we profile HIF-1?-interacting proteins using proteomics analysis and identify fatty acid-binding protein 5 (FABP5) as a critical HIF-1?-binding partner. In hepatocellular carcinoma (HCC) tissues, both FABP5 and HIF-1? are upregulated, and their expression levels are associated with poor prognosis. FABP5 enhances HIF-1? activity by promoting HIF-1? synthesis while disrupting FIH/HIF-1? interaction at the same time. Oleic-acid treatment activates the FABP5/HIF-1? axis, thereby promoting lipid accumulation and cell proliferation in HCC cells. Our results indicate that fatty-acid-induced FABP5 upregulation drives HCC progression through HIF-1-driven lipid metabolism reprogramming.

SUBMITTER: Seo J 

PROVIDER: S-EPMC7599230 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature