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.
A Systems Biology Approach to Understanding the Pathophysiology of High-Grade Serous Ovarian Cancer: Focus on Iron and Fatty Acid Metabolism