Autophagy promotes BrafV600E-driven lung tumorigenesis by preserving mitochondrial metabolism

Anne M. Strohecker, Eileen White

Research output: Contribution to journalShort surveypeer-review

65 Scopus citations


The role of autophagy in cancer is complex and context-dependent. Here we describe work with genetically engineered mouse models of non-small cell lung cancer (NSCLC) in which the tumor-suppressive and tumor-promoting function of autophagy can be visualized in the same system. We discovered that early tumorigenesis in BrafV600E-driven lung cancer is accelerated by autophagy ablation due to unmitigated oxidative stress, as observed with loss of Nfe2l2/Nrf2-mediated antioxidant defense. However, this growth advantage is eventually overshadowed by progressive mitochondrial dysfunction and metabolic insufficiency, and is associated with increased survival of mice bearing autophagy-deficient tumors. Atg7 deficiency alters progression of Braf V600E-driven tumors from adenomas (BrafV600E; atg7 -/-) and adenocarcinomas (trp53-/-; BrafV600E; atg7-/-) to benign oncocytomas that accumulated morphologically and functionally defective mitochondria, suggesting that defects in mitochondrial metabolism may compromise continued tumor growth. Analysis of tumor-derived cell lines (TDCLs) revealed that Atg7-deficient cells are significantly more sensitive to starvation than Atg7-wild-type counterparts, and are impaired in their ability to respire, phenotypes that are rescued by the addition of exogenous glutamine. Taken together, these data suggest that Braf V600E-driven tumors become addicted to autophagy as a means to preserve mitochondrial function and glutamine metabolism, and that inhibiting autophagy may be a powerful strategy for BrafV600E-driven malignancies.

Original languageEnglish (US)
Pages (from-to)384-385
Number of pages2
Issue number2
StatePublished - Feb 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


  • Autophagy
  • Braf
  • Glutamine
  • Metabolism
  • Oncocytoma


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