Malate targets pyruvate kinase M2 to promote colorectal cancer cell cycle arrest and tumor suppression.

ABSTRACT: To survive nutrient stress caused by rapid proliferation and dysfunctional vasculature, tumor cells extensively reprogram their metabolic pathways, including the tricarboxylic acid (TCA) cycle representing a critical remodeling node. Functioning as a key TCA cycle intermediate, malate bridges fumarate and oxaloacetate, both of which are metabolites known to play significant roles in tumorigenesis. However, whether malate itself regulates tumor progression and the specific mechanism remain unclear. In this study, we demonstrate that oral administration of malate significantly inhibits the growth of colorectal cancer (CRC) xenografts in both nude mice and immunocompetent models, suggesting its antitumor effects are immunity-independent. Mechanistically, we found that malate acts as an allost

SUBMITTER: Zhao K 

PROVIDER: S-EPMC12515184 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature