Abstract
Hypoxia-inducible factor-1 alpha (HIF-1α) 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-1α to this process remains elusive. In this study, we profile HIF-1α-interacting proteins using proteomics analysis and identify fatty acid-binding protein 5 (FABP5) as a critical HIF-1α-binding partner. In hepatocellular carcinoma (HCC) tissues, both FABP5 and HIF-1α are upregulated, and their expression levels are associated with poor prognosis. FABP5 enhances HIF-1α activity by promoting HIF-1α synthesis while disrupting FIH/HIF-1α interaction at the same time. Oleic-acid treatment activates the FABP5/HIF-1α 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ascorbic Acid / pharmacology
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / mortality
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Carcinoma, Hepatocellular / pathology*
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cytosol / metabolism
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Fatty Acid-Binding Proteins / genetics
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Fatty Acid-Binding Proteins / metabolism*
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Gene Expression Regulation, Neoplastic
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Hep G2 Cells
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Lipid Metabolism / drug effects
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism
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Liver Neoplasms / mortality
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Liver Neoplasms / pathology*
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Mixed Function Oxygenases / metabolism
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Oleic Acid / pharmacology
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Repressor Proteins / metabolism
Substances
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FABP5 protein, human
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Fatty Acid-Binding Proteins
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Repressor Proteins
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Oleic Acid
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Mixed Function Oxygenases
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HIF1AN protein, human
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Ascorbic Acid