Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras -driven cancers

Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently. NSCLC tumors incorporate free BCAAs into tissue protein and use BCAAs as a nitrogen source, whereas PDAC tumors have decreased BCAA uptake. These differences are reflected in…

• BW
  Burroughs Wellcome Fund
• DR
  Damon Runyon Cancer Research Foundation

  Award: DRG-2241-15
• LF
  Lustgarten Foundation
• SU
  Stand Up To Cancer
• NC
  National Cancer Institute

  Awards: P30CA1405141, R01CA201276, R01CA168653
• NI
  National Institute of General Medical Sciences

  Award: T32GM007753