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 alter mitochondrial
pyruvate oxidation compared to lung
tumors with intact Rb1. Additional tracer studies using [U-13C,15N]-
glutamine and [U-13C]-
lactate demonstrated that loss of Rb1 did not alter glutaminolysis or utilization of circulating
lactate within the tricarboxylic acid cycle (TCA) in vivo. Taken together, these data suggest that the loss of Rb1 promotes a glycolytic phenotype, while not altering
pyruvate oxidative metabolism or
glutamine anaplerosis in Kras-driven lung
tumors.