Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in…

• NS
  National Science Foundation

  Awards: 0447479, 0132295, EPS-0447479
• UO
  University of Louisville

  Award: 20044
• NI
  National Institutes of Health

  Awards: 1U24DK097215-01A1, P01CA163223-01A1, P01CA163223, 1R01ES022191-01, 1R01CA118434-01A2
• NC
  National Center for Research Resources
• OO
  Office of Experimental Program to Stimulate Competitive Research