Acetyl-CoA Synthetase 2 as a Therapeutic Target in Tumor Metabolism

Acetyl-CoA Synthetase 2 (ACSS2) belongs to a member of the acyl-CoA short-chain synthase family, which can convert acetate in the cytoplasm and nucleus into acetyl-CoA. It has been proven that ACSS2 is highly expressed in glioblastoma, breast cancer, liver cancer, prostate cancer, bladder cancer, renal cancer, and other tumors, and is closely related to tumor stage and the overall survival rate of patients. Accumulating studies show that hypoxia and a low serum level induce ACSS2 expression to help tumor cells cope with this nutrient-poor environment. The potential mechanisms are associated with the ability of ACSS2 to promote the synthesis of lipids in the cytoplasm, induce the acetylation of histones in the nucleus, and facilitate the expression of autophagy genes. Novel-specific inhibitors of ACSS2 are developed and confirmed to the effectiveness in pre-clinical tumor models. Targeting ACSS2 may provide novel approaches for tumor treatment. This review summarizes the biological function of ACSS2, its relation to survival and prognosis in different tumors, and how ACSS2 mediates different pathways to promote tumor metastasis, invasion, and drug resistance.