ATP-citrate lyase: carcinogenesis and therapeutic advances

ATP citrate lyase (ACLY) is involved in acetyl-coenzyme A synthesis and protein acetylation, thereby increasing lipid metabolism and altering protein metabolism to affect cellular metabolism. Additionally, ACLY is associated with various biological and pathological functions, especially regarding tumorigenesis. It facilitates the progression of various cancer types, including liver, lung, breast, prostate, and colorectal cancers. Mechanisms underlying ACLY-mediated carcinogenesis are under investigation and may not be limited to energy metabolism and biosynthesis. Acetylation modification of specific signaling molecules and transcription factors is considered a potential mechanism of ACLY-mediated tumorigenesis and offers novel insights and potential targets for the clinical treatment of tumors. Furthermore, the antitumor effect of pharmacological ACLY-inhibiting agents, including various small molecules or naturally active compounds, has been reported, albeit their practical application in clinical settings remains limited. This study aims to comprehensively review the oncogenic role of ACLY, with a focus on major collaborators and regulatory genes.