Loss of Rb1 enhances glycolytic metabolism in kras-driven lung tumors in vivo

Lindsey R. Conroy, Susan Dougherty, Traci Kruer, Stephanie Metcalf, Pawel Lorkiewicz, Liqing He, Xinmin Yin, Xiang Zhang, Sengodagounder Arumugam, Lyndsay E.A. Young, Ramon C. Sun, Brian F. Clem

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 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.

Original languageEnglish
Article number237
JournalCancers
Volume12
Issue number1
DOIs
StatePublished - Jan 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Glycolysis
  • Lung cancer
  • Metabolomics
  • Rb1
  • TCA anaplerosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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