Dylgjeri E, Kothari V, Shafi AA, Semenova G, Gallagher PT, Guan YF, Pang A, Goodwin JF, Irani S, McCann JJ, Mandigo AC, Chand S, McNair CM, Vasilevskaya I, Schiewer MJ, Lallas CD, McCue PA, Gomella LG, Seifert EL, Carroll JS, Butler LM, Holst J, Kelly WK, Knudsen KE. A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration Resistant Prostate Cancer. Clin Cancer Res. 2022 Jan 25:clincanres.1846.2021. doi: 10.1158/1078-0432.CCR-21-1846. Online ahead of print.PMID: 35078861
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Unbiased proteomic and metabolomic approaches in clinically relevant tumor models uncovered a novel role of DNA-PK in metabolic regulation of cancer progression. DNA-PK regulation of metabolism was interrogated using pharmacological and genetic perturbation using in vitro cell models, in vivo xenografts, and ex vivo in patient-derived explants (PDE).

Findings herein unveil novel DNA-PK partners, substrates, and function in PCa. The role of DNA-PK impacts glycolysis through direct interaction with glycolytic enzymes and modulation of enzymatic activity. These events support energy production that may contribute to generation and/or maintenance of DNA-PK-mediated aggressive disease phenotypes.