Cancer cells adapt to nutrient-deprived tumor microenvironment during progression via regulating the level and function of metabolic
enzymes.
Acetyl-coenzyme A (AcCoA) is a key metabolic intermediate that is crucial for
cancer cell metabolism, especially under metabolic stress. It is of special significance to decipher the role
acetyl-CoA synthetase short chain family (ACSS) in
cancer cells confronting metabolic stress. Here we analyzed the generation of lipogenic AcCoA in
bladder cancer cells under metabolic stress and found that in bladder urothelial
carcinoma (BLCA) cells, the proportion of lipogenic AcCoA generated from
glucose were largely reduced under metabolic stress. Our results revealed that ACSS3 was responsible for lipogenic AcCoA synthesis in BLCA cells under metabolic stress. Interestingly, we found that ACSS3 was required for
acetate utilization and
histone acetylation. Moreover, our data illustrated that ACSS3 promoted BLCA cell growth. In addition, through analyzing clinical samples, we found that both
mRNA and
protein levels of ACSS3 were dramatically upregulated in BLCA samples in comparison with adjacent controls and BLCA patients with lower ACSS3 expression were entitled with longer overall survival. Our data revealed an oncogenic role of ACSS3 via regulating AcCoA generation in BLCA and provided a promising target in metabolic pathway for BLCA treatment.