title: Tumor-promoting and -suppressive roles of autophagy in the same mouse model of BrafV600E-driven lung cancer.
abstract: Although a role of autophagy in cancer development and progression has received increasing appreciation in recent years, there are still significantly uncertain and conflicting results about its tumor-suppressive and -promoting functions, and, more importantly, a lack of understanding of mechanisms underlying these opposing activities. The work presented by Strohecker and colleagues uses an innovative approach to address these challenges by examining the effects of inactivating the key autophagy gene Atg7 at different stages of oncogenic development in a BrafV600E-driven mouse lung cancer model. The authors show that autophagy blockage initially accelerated tumor development, but suppressed tumor progression in later stages, converting adenomas to oncocytomas and increasing mouse survival. Importantly, they identify a critical role of glutamine dependency in the suppression of BrafV600E-induced cancer, thus revealing an important mechanism by which autophagy may promote tumor progression in different cellular contexts.
authors.affiliation: 1Divisions of Molecular Medicine and Genetics, Department of Internal Medicine, and 2Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D005973:Glutamine; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D000071193:Autophagy-Related Protein 7