Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation.
Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation.
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DOI：
10.1038/s41388-021-01667-y
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发表时间：
2021-03
期刊：
影响因子：
8
通讯作者：
Cai H
中科院分区：
文献类型：
--
作者：
Ma Y;Zha J;Yang X;Li Q;Zhang Q;Yin A;Beharry Z;Huang H;Huang J;Bartlett M;Ye K;Yin H;Cai H
脂肪酸代谢对细胞成分的生物生成和ATP的产生至关重要，以维持癌细胞的增殖。长链脂肪酸酰基辅酶a合成酶（acsl）是脂肪酸代谢中的一组限速酶，它催化外源或新合成的脂肪酸转化为相应的脂肪酸酰基辅酶a。本研究通过对ACSLs水平和脂肪酰基辅酶a量的系统分析发现，ACSL1与广谱脂肪酰基辅酶a水平显著相关，且在人前列腺肿瘤中升高。ACSL1增加了脂肪酰基辅酶a的生物合成，包括C16:0-， C18:0-， C18:1-和c18:2-辅酶a，甘油三酯和脂质积累。在机制上，ACSL1通过调节CPT1活性来调节线粒体呼吸、β-氧化和ATP的产生。ACSL1基因的下调可抑制细胞周期，抑制体外前列腺癌细胞的增殖和迁移，抑制体内前列腺异种移植肿瘤的生长。本研究提示ACSL1在前列腺肿瘤进展中发挥重要作用，为前列腺癌的治疗提供了一种靶向脂肪酸代谢的治疗策略。
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.
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影响因子：
5.7
作者：
Kuemmerle NB;Rysman E;Lombardo PS;Flanagan AJ;Lipe BC;Wells WA;Pettus JR;Froehlich HM;Memoli VA;Morganelli PM;Swinnen JV;Timmerman LA;Chaychi L;Fricano CJ;Eisenberg BL;Coleman WB;Kinlaw WB
通讯作者：
Kinlaw WB
影响因子：
5.6
作者：
Koizume S;Miyagi Y
通讯作者：
Miyagi Y
影响因子：
29
作者：
Yue S;Li J;Lee SY;Lee HJ;Shao T;Song B;Cheng L;Masterson TA;Liu X;Ratliff TL;Cheng JX
通讯作者：
Cheng JX
影响因子：
2.9
作者：
BIEBER, LL;ABRAHAM, T;HELMRATH, T
通讯作者：
HELMRATH, T
影响因子：
8
作者：
Wang, Yuan Yuan;Attane, Camille;Muller, Catherine
通讯作者：
Muller, Catherine