Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation
| Autor: | Kaixiong Ye, Amelia Yin, Qianjin Li, Qingfu Zhang, Junyi Zha, Zanna Beharry, Yongjie Ma, Jiaoti Huang, Xiangkun Yang, Hanwen Huang, Houjian Cai, Hang Yin, Michael G. Bartlett |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Cancer Research Biology Fatty acid beta-oxidation Mice 03 medical and health sciences Prostate cancer chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Biosynthesis Cell Line Tumor Coenzyme A Ligases Genetics medicine Animals Humans Molecular Biology Cell Proliferation chemistry.chemical_classification Fatty acid metabolism Lipogenesis Fatty Acids Prostatic Neoplasms medicine.disease 030104 developmental biology Enzyme Biochemistry chemistry Tumor progression 030220 oncology & carcinogenesis Cancer cell Disease Progression Heterografts lipids (amino acids peptides and proteins) Oxidation-Reduction |
| Zdroj: | Oncogene. 40:1806-1820 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-021-01667-y |
| Popis: | Fatty acid metabolism is essential for the biogenesis of cellular components and ATP production to sustain proliferation of cancer cells. Long-chain fatty acyl-CoA synthetases (ACSLs), a group of rate-limiting enzymes in fatty acid metabolism, catalyze the bioconversion of exogenous or de novo synthesized fatty acids to their corresponding fatty acyl-CoAs. In this study, systematical analysis of ACSLs levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors. ACSL1 increased the biosynthesis of fatty acyl-CoAs including C16:0-, C18:0-, C18:1-, and C18:2-CoA, triglycerides and lipid accumulation in cancer cells. Mechanistically, ACSL1 modulated mitochondrial respiration, β-oxidation, and ATP production through regulation of CPT1 activity. Knockdown of ACSL1 inhibited the cell cycle, and suppressed the proliferation and migration of prostate cancer cells in vitro, and growth of prostate xenograft tumors in vivo. Our study implicates ACSL1 as playing an important role in prostate tumor progression, and provides a therapeutic strategy of targeting fatty acid metabolism for the treatment of prostate cancer. |
| Databáze: | OpenAIRE |
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