title: Targeting CPT1A enhances metabolic therapy in human melanoma cells with the BRAF V600E mutation.
abstract: Cancer cells are characterized by altered metabolic processes. Recent evidence of metabolic alterations has indicated that the fatty acid oxidation (FAO) pathway is used as a carbon source for anabolic processes in some tumors, thus making this pathway a potential target for therapy. The carnitine palmitoyltransferase (CPT; EC 2.3.1.21) enzyme transfers long-chain fatty acids from the cytosol to the mitochondrial matrix for β-oxidation. Because carnitine palmitoyl transferase 1a (CPT1a) is the rate-limiting enzyme for FAO, the authors evaluated the effects of CPT1A knock-down in BRAF V600E melanoma cell lines. The results showed that knock-down of CPT1A inhibited FAO and that CPT1A is critical for malignant V600E melanoma cells, particularly BRAF V600E melanoma cells. The proliferation and tumorigenesis in V600E melanoma were decrease after CPT1A knockdown. These results suggest that therapy for BRAF V600E melanoma can include targeting metabolic alterations. CPT1A is more important for lipid synthesis in V600E mutant melanoma cells than in wild-type BRAF melanoma cells.
authors: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors: Gi-Jun
authors: GJ
authors: Sung
authors: Division of Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do, South Korea.
authors: Hyo-Kyoung
authors: HK
authors: Choi
authors: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors: Sungmin
authors: S
authors: Kwak
authors: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
authors: Ji-Hye
authors: JH
authors: Song
authors: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankuk University College of Medicine, Seoul, South Korea.
authors: Hyeonseok
authors: H
authors: Ko
authors: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Brain Korea 21 Project for Medical Sciences, Severance Medical Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors: Ho-Geun
authors: HG
authors: Yoon
authors: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: heebum@gmail.com.
authors: Hee-Bum
authors: HB
authors: Kang
authors: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: choikc75@amc.seoul.kr.
authors: Kyung-Chul
authors: KC
authors: Choi
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D058990:Molecular Targeted Therapy; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; CPT1A; Fatty acid oxidation; Lipid synthesis; Melanoma; Proliferation