Loss of Rb1 Enhances Glycolytic Metabolism in Kras-Driven Lung Tumors In Vivo.

ABSTRACT: Dysregulated metabolism is a hallmark of cancer cells and is driven in part by specific genetic alterations in various oncogenes or tumor suppressors. The retinoblastoma protein (pRb) is a tumor suppressor that canonically regulates cell cycle progression; however, recent studies have highlighted a functional role for pRb in controlling cellular metabolism. Here, we report that loss of the gene encoding pRb (Rb1) in a transgenic mutant Kras-driven model of lung cancer results in metabolic reprogramming. Our tracer studies using bolus dosing of [U-13C]-glucose revealed an increase in glucose carbon incorporation into select glycolytic intermediates. Consistent with this result, Rb1-depleted tumors exhibited increased expression of key glycolytic enzymes. Interestingly, loss of Rb1 did not a

SUBMITTER: Conroy LR 

PROVIDER: S-EPMC7016860 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature