Citrate Promotes Excessive Lipid Biosynthesis and Senescence in Tumor Cells for Tumor Therapy.

ABSTRACT: Metabolic disorder is one of the hallmarks of cancers, and reprogramming of metabolism is becoming a novel strategy for cancer treatment. Citrate is a key metabolite and critical metabolic regulator linking glycolysis and lipid metabolism in cellular energy homeostasis. Here it is reported that citrate treatment (both sodium citrate and citric acid) significantly suppresses tumor cell proliferation and growth in various tumor types. Mechanistically, citrate promotes excessive lipid biosynthesis and induces disruption of lipid metabolism in tumor cells, resulting in tumor cell senescence and growth inhibition. Furthermore, ATM-associated DNA damage response cooperates with MAPK and mTOR signaling pathways to control citrate-induced tumor cell growth arrest and senescence. In vivo studies fu

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC8728847 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature