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

• Published in: Cancers Vol. 12; no. 1; p. 237
• Main Authors: Conroy, Lindsey R, Dougherty, Susan, Kruer, Traci, Metcalf, Stephanie, Lorkiewicz, Pawel, He, Liqing, Yin, Xinmin, Zhang, Xiang, Arumugam, Sengodagounder, Young, Lyndsay E A, Sun, Ramon C, Clem, Brian F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.01.2020; MDPI
• Subjects: Cancer; Carbon; Cell cycle; Dehydrogenases; Dosage; Enzymes; Gene expression; Glucose; Glutamine; Glycolysis; Intermediates; K-Ras protein; Kinases; Labeling; Lactic acid; Lung cancer; Metabolism; Metabolites; Mitochondria; Oxidation; Oxidative metabolism; Phenotypes; Plasma; Pyruvic acid; Retina; Retinoblastoma; Retinoblastoma protein; Transcription factors; Tricarboxylic acid cycle; Tumor suppressor genes; Tumors; Rb1; lung cancer; TCA anaplerosis; metabolomics; glycolysis
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12010237

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 ( ) in a transgenic mutant -driven model of lung cancer results in metabolic reprogramming. Our tracer studies using bolus dosing of [U- C]-glucose revealed an increase in glucose carbon incorporation into select glycolytic intermediates. Consistent with this result, -depleted tumors exhibited increased expression of key glycolytic enzymes. Interestingly, loss of did not alter mitochondrial pyruvate oxidation compared to lung tumors with intact . Additional tracer studies using [U- C, N]-glutamine and [U- C]-lactate demonstrated that loss of 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 promotes a glycolytic phenotype, while not altering pyruvate oxidative metabolism or glutamine anaplerosis in -driven lung tumors.