Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors

作者：Guo Jessie Yanxiang; White Eileen^*

来源：Autophagy, 2013, 9(10): 1636-1638.

DOI：10.4161/auto.26123

• autophagy
• KRAS
• NSCLC
• metabolism
• mitochondria
• oncocytoma
• p53
• fatty acid oxidation

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.

• 出版日期2013-10-1