HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer.
HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer.
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DOI：
10.1155/2021/6610529
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发表时间：
2021
影响因子：
--
通讯作者：
Zhan X
中科院分区：
文献类型：
--
作者：
Li N;Li N;Wen S;Li B;Zhang Y;Liu Q;Zheng S;Yang J;Shen L;Xing L;Zhan X
越来越多的证据表明，癌症是一种与氧化应激相关的疾病，而氧化应激与热休克蛋白（HSP）密切相关。脂质氧化应激源自脂质代谢失调，与恶性肿瘤的发生、发展密切相关。本研究旨在探讨热休克蛋白在卵巢癌脂肪酸代谢异常中的调节作用。对卵巢癌中 5115 个线粒体表达蛋白的通路网络分析揭示了各种脂质代谢通路的改变，包括脂肪酸降解、脂肪酸代谢、丁酸代谢和丙酸代谢。 HSP60 调节这些脂质代谢途径中脂质代谢蛋白的表达，包括 ADH5、ECHS1、EHHADH、HIBCH、SREBP1、ACC1 和 ALDH2。此外，干扰 HSP60 表达可抑制体外卵巢癌细胞的迁移、增殖和细胞周期并诱导其凋亡。此外，线粒体磷酸化蛋白质组学和免疫沉淀-蛋白质印迹实验发现并证实HSP60蛋白中Ser70残基发生磷酸化，这可能调节卵巢癌中ALDH2和ACADS的蛋白折叠。这些结果清楚地表明，氧化应激相关的卵巢癌中存在脂质代谢异常，HSP60及其磷酸化可能调节卵巢癌中的脂质代谢异常。它为人类卵巢癌的脂质代谢重编程开辟了新的视野。
Accumulating evidence demonstrates that cancer is an oxidative stress-related disease, and oxidative stress is closely linked with heat shock proteins (HSPs). Lipid oxidative stress is derived from lipid metabolism dysregulation that is closely associated with the development and progression of malignancies. This study sought to investigate regulatory roles of HSPs in fatty acid metabolism abnormality in ovarian cancer. Pathway network analysis of 5115 mitochondrial expressed proteins in ovarian cancer revealed various lipid metabolism pathway alterations, including fatty acid degradation, fatty acid metabolism, butanoate metabolism, and propanoate metabolism. HSP60 regulated the expressions of lipid metabolism proteins in these lipid metabolism pathways, including ADH5, ECHS1, EHHADH, HIBCH, SREBP1, ACC1, and ALDH2. Further, interfering HSP60 expression inhibited migration, proliferation, and cell cycle and induced apoptosis of ovarian cancer cells in vitro. In addition, mitochondrial phosphoproteomics and immunoprecipitation-western blot experiments identified and confirmed that phosphorylation occurred at residue Ser70 in protein HSP60, which might regulate protein folding of ALDH2 and ACADS in ovarian cancers. These findings clearly demonstrated that lipid metabolism abnormality occurred in oxidative stress-related ovarian cancer and that HSP60 and its phosphorylation might regulate this lipid metabolism abnormality in ovarian cancer. It opens a novel vision in the lipid metabolism reprogramming in human ovarian cancer.
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影响因子：
28.5
作者：
Li X;Fang P;Mai J;Choi ET;Wang H;Yang XF
通讯作者：
Yang XF
影响因子：
5.2
作者：
Li, Na;Qian, Shehua;Zhan, Xianquan
通讯作者：
Zhan, Xianquan
影响因子：
1.5
作者：
Makino, Toshihiko;Ishikawa, Kayoko;Nakayama, Hiroyuki
通讯作者：
Nakayama, Hiroyuki
影响因子：
9.7
作者：
Castle, PE;Ashfaq, R;Muller, CY
通讯作者：
Muller, CY
影响因子：
5
作者：
Dessein, Anne-Frederique;Fontaine, Monique;Vamecq, Joseph
通讯作者：
Vamecq, Joseph