Title |
A dual role for autophagy in a murine model of lung cancer
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Published in |
Nature Communications, January 2014
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DOI | 10.1038/ncomms4056 |
Pubmed ID | |
Authors |
Shuan Rao, Luigi Tortola, Thomas Perlot, Gerald Wirnsberger, Maria Novatchkova, Roberto Nitsch, Peter Sykacek, Lukas Frank, Daniel Schramek, Vukoslav Komnenovic, Verena Sigl, Karin Aumayr, Gerald Schmauss, Nicole Fellner, Stephan Handschuh, Martin Glösmann, Pawel Pasierbek, Michaela Schlederer, Guenter P. Resch, Yuting Ma, Heng Yang, Helmuth Popper, Lukas Kenner, Guido Kroemer, Josef M. Penninger |
Abstract |
Autophagy is a mechanism by which starving cells can control their energy requirements and metabolic states, thus facilitating the survival of cells in stressful environments, in particular in the pathogenesis of cancer. Here we report that tissue-specific inactivation of Atg5, essential for the formation of autophagosomes, markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage of tumour-bearing mice. Autophagy-defective lung cancers exhibit impaired mitochondrial energy homoeostasis, oxidative stress and a constitutively active DNA damage response. Genetic deletion of the tumour suppressor p53 reinstates cancer progression of autophagy-deficient tumours. Although there is improved survival, the onset of Atg5-mutant KRas(G12D)-driven lung tumours is markedly accelerated. Mechanistically, increased oncogenesis maps to regulatory T cells. These results demonstrate that, in KRas(G12D)-driven lung cancer, Atg5-regulated autophagy accelerates tumour progression; however, autophagy also represses early oncogenesis, suggesting a link between deregulated autophagy and regulatory T cell controlled anticancer immunity. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Hungary | 1 | <1% |
Germany | 1 | <1% |
Czechia | 1 | <1% |
United Kingdom | 1 | <1% |
Mexico | 1 | <1% |
Belgium | 1 | <1% |
China | 1 | <1% |
Unknown | 248 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 58 | 23% |
Researcher | 45 | 18% |
Student > Master | 25 | 10% |
Student > Bachelor | 23 | 9% |
Student > Doctoral Student | 14 | 5% |
Other | 34 | 13% |
Unknown | 56 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 85 | 33% |
Agricultural and Biological Sciences | 42 | 16% |
Medicine and Dentistry | 22 | 9% |
Immunology and Microbiology | 13 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 4% |
Other | 23 | 9% |
Unknown | 61 | 24% |