Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer subtype, characterized by a lipid storage phenotype. We found that carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme of mitochondrial fatty acid (FA) transport, is repressed by hypoxia-inducible factors (HIFs), reducing FA oxidation (FAO). Altering lipid metabolism may be a new therapeutic avenue in ccRCC.
Keywords:
CPT1A; HIF; ccRCC; clear cell renal cell carcinoma; hypoxia; lipid metabolism.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Carcinoma, Renal Cell / drug therapy*
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Carcinoma, Renal Cell / genetics
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Carcinoma, Renal Cell / pathology
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Carnitine O-Palmitoyltransferase / antagonists & inhibitors*
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Carnitine O-Palmitoyltransferase / metabolism
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Fatty Acids / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Kidney Neoplasms / drug therapy*
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Kidney Neoplasms / genetics
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Kidney Neoplasms / pathology
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Lipid Droplets / metabolism
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Lipid Metabolism / drug effects*
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Lipid Metabolism / genetics
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mutation
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Oxidation-Reduction / drug effects
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Peroxisomes / drug effects
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Peroxisomes / metabolism
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Proteolysis
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Tumor Hypoxia / genetics
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Von Hippel-Lindau Tumor Suppressor Protein / genetics
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Von Hippel-Lindau Tumor Suppressor Protein / metabolism
Substances
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Antineoplastic Agents
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Basic Helix-Loop-Helix Transcription Factors
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Fatty Acids
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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endothelial PAS domain-containing protein 1
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CPT1A protein, human
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Carnitine O-Palmitoyltransferase
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Von Hippel-Lindau Tumor Suppressor Protein
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VHL protein, human