title: Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors.
abstract: Evidence suggests that the role of autophagy in tumorigenesis is context dependent. Using genetically engineered mouse models (GEMMs) for human non-small-cell lung cancer (NSCLC), we found that deletion of the essential autophagy gene, Atg7, in KRAS(G12D)-driven NSCLC inhibits tumor growth and converts adenomas and adenocarcinomas to benign oncocytomas characterized by the accumulation of respiration-defective mitochondria. Atg7 is required to preserve mitochondrial fatty acid oxidation (FAO) to maintain lipid homeostasis upon additional loss of Trp53 in NSCLC. Furthermore, cell lines derived from autophagy-deficient tumors depend on glutamine to survive starvation. This suggests that autophagy is essential for the metabolism, growth, and fate of NSCLC.
authors: Rutgers Cancer Institute of New Jersey; New Brunswick, NJ USA; Department of Molecular Biology and Biochemistry; Rutgers University; Piscataway, NJ USA.
authors: Jessie Yanxiang
authors: JY
authors: Guo
authors: Rutgers Cancer Institute of New Jersey; New Brunswick, NJ USA; Department of Molecular Biology and Biochemistry; Rutgers University; Piscataway, NJ USA.
authors: Eileen
authors: E
authors: White
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS; NSCLC; autophagy; fatty acid oxidation; metabolism; mitochondria; oncocytoma; p53