脂滴(lipid droplets)是细胞内脂质贮存和调节细胞脂质稳态的重要细胞器,其表面具有多种脂滴相关蛋白质。长链酰基辅酶A合成酶家族的成员脂酰辅酶A长链合成酶3(acyl CoA long chain synthetase 3,ACSL3)即脂滴相关蛋白质的一种,也是生...脂滴(lipid droplets)是细胞内脂质贮存和调节细胞脂质稳态的重要细胞器,其表面具有多种脂滴相关蛋白质。长链酰基辅酶A合成酶家族的成员脂酰辅酶A长链合成酶3(acyl CoA long chain synthetase 3,ACSL3)即脂滴相关蛋白质的一种,也是生物合成过程中必需的酶之一。ACSL3广泛分布于大多数细胞中的脂滴表面,其在脂滴的合成、自噬的调节和细胞铁死亡等多种病理生理过程中发挥着不同的作用。此外,多项研究表明,ACSL3还广泛参与到多种疾病的发生发展,包括动脉粥样硬化、非酒精性脂肪肝病、糖尿病和肿瘤等。当前,国内对ACSL3的研究相对集中于ACSL3与动物育种和生长的关系,而对ACSL3在脂质代谢中的作用机制及其与疾病的关系鲜有报道。本文基于国内外对ACSL3的研究,对该基因的结构、在细胞脂代谢中的作用机制及其相关疾病进行归纳,进一步探究ACSL3在脂滴的合成、自噬、铁死亡过程中的作用,为防治动脉粥样硬化、非酒精性脂肪肝病、糖尿病(glucose)等多种ACSL3相关疾病提供新的理论依据。展开更多
Metastasis is the main cause of cancer-specific death in patients with prostate cancer(PCa).Acyl-coenzyme A synthetase long-chain family member 3(ACSL3)is involved in the metabolic reprogramming of multiple types of c...Metastasis is the main cause of cancer-specific death in patients with prostate cancer(PCa).Acyl-coenzyme A synthetase long-chain family member 3(ACSL3)is involved in the metabolic reprogramming of multiple types of cancer cells,but its role in PCa metastasis remains largely unknown.Here,we determined the effect of overexpression or small interfering RNA-mediated depletion of ACSL3 on the migratory and invasive abilities of human PCa cell lines.We also conducted phospho-protein microarray analysis to identify signaling pathway components affected by ACSL3 modulation.Overexpression of ACSL3 promoted the migration and invasion of PCa cells,whereas ACSL3 downregulation had the opposite effects.Mechanistically,phospho-protein analysis showed that ACSL3 regulated the phosphorylation of AKT and the expression of matrix metalloproteinase9.Our results support a potential role for ACSL3 in promoting the metastatic behavior of PCa,possibly via AKT/matrix metalloproteinase9 pathways.Thus,ACSL3 could be a novel target for the development of treatments for PCa.展开更多
文摘脂滴(lipid droplets)是细胞内脂质贮存和调节细胞脂质稳态的重要细胞器,其表面具有多种脂滴相关蛋白质。长链酰基辅酶A合成酶家族的成员脂酰辅酶A长链合成酶3(acyl CoA long chain synthetase 3,ACSL3)即脂滴相关蛋白质的一种,也是生物合成过程中必需的酶之一。ACSL3广泛分布于大多数细胞中的脂滴表面,其在脂滴的合成、自噬的调节和细胞铁死亡等多种病理生理过程中发挥着不同的作用。此外,多项研究表明,ACSL3还广泛参与到多种疾病的发生发展,包括动脉粥样硬化、非酒精性脂肪肝病、糖尿病和肿瘤等。当前,国内对ACSL3的研究相对集中于ACSL3与动物育种和生长的关系,而对ACSL3在脂质代谢中的作用机制及其与疾病的关系鲜有报道。本文基于国内外对ACSL3的研究,对该基因的结构、在细胞脂代谢中的作用机制及其相关疾病进行归纳,进一步探究ACSL3在脂滴的合成、自噬、铁死亡过程中的作用,为防治动脉粥样硬化、非酒精性脂肪肝病、糖尿病(glucose)等多种ACSL3相关疾病提供新的理论依据。
基金Financial support This work was supported by the Pearl River S&T Nova Program of Guangzhou,China(no.201710010039)the Natural Science Foundation of Guangdong Province,China(no.2015A030313031 and 2017A030313898)+2 种基金the Science and Technology Program of Guangdong Province,China(no.2017A020215028)the Science and Technology Program of Guangzhou(no.201707010113)and the Basic Service Charge Young Teachers Cultivation Project of Sun Yat-sen University,China(no.17ykpy48).
文摘Metastasis is the main cause of cancer-specific death in patients with prostate cancer(PCa).Acyl-coenzyme A synthetase long-chain family member 3(ACSL3)is involved in the metabolic reprogramming of multiple types of cancer cells,but its role in PCa metastasis remains largely unknown.Here,we determined the effect of overexpression or small interfering RNA-mediated depletion of ACSL3 on the migratory and invasive abilities of human PCa cell lines.We also conducted phospho-protein microarray analysis to identify signaling pathway components affected by ACSL3 modulation.Overexpression of ACSL3 promoted the migration and invasion of PCa cells,whereas ACSL3 downregulation had the opposite effects.Mechanistically,phospho-protein analysis showed that ACSL3 regulated the phosphorylation of AKT and the expression of matrix metalloproteinase9.Our results support a potential role for ACSL3 in promoting the metastatic behavior of PCa,possibly via AKT/matrix metalloproteinase9 pathways.Thus,ACSL3 could be a novel target for the development of treatments for PCa.
