Branched-Chain α Keto-Acid Dehydrogenase Kinase-Mediated AKT Phosphorylation Promotes RCC Tumorigenesis and Drug Resistance.

ABSTRACT: Advanced renal cell carcinoma (RCC) primarily relies on targeted and immune-based therapies, yet these treatments often face limitations due to inefficacy and drug resistance. Branched-chain α-keto-acid dehydrogenase kinase (BCKDK) has been implicated in promoting RCC metastasis, but its specific substrates and the mechanisms underlying its regulation of RCC progression remain poorly understood. This study uncovers a novel mechanism whereby BCKDK-mediated AKT phosphorylation drives RCC tumorigenesis and drug resistance. Elevated BCKDK expression correlates with poor prognosis in RCC clinical samples. BCKDK deficiency inhibits RCC cell proliferation and tumorigenesis both in vitro and in vivo. Mechanistic investigations reveal that BCKDK directly binds to and regulates the phosphorylation o

SUBMITTER: Tian Q 

PROVIDER: S-EPMC12561327 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature