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Autophagy in malignant transformation and cancer progression
Authors:Ravi K Amaravadi  Eric H Baehrecke  Francesco Cecconi  Patrice Codogno  Jayanta Debnath  David A Gewirtz  Vassiliki Karantza  Alec Kimmelman  Sharad Kumar  Beth Levine  Maria Chiara Maiuri  Seamus J Martin  Josef Penninger  Mauro Piacentini  David C Rubinsztein  Hans‐Uwe Simon  Anne Simonsen  Andrew M Thorburn  Guillermo Velasco  Guido Kroemer
Affiliation:1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA;2. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA;3. Cell Stress and Survival Unit, Danish Cancer Society Research Center, Copenhagen, Denmark;4. IRCCS Fondazione Santa Lucia and Department of Biology, University of Rome Tor Vergata, Rome, Italy;5. Université Paris Descartes, Sorbonne Paris Cité, Paris, France;6. Institut Necker Enfants‐Malades (INEM), Paris, France;7. INSERM, U1151, Paris, France;8. CNRS, UMR8253, Paris, France;9. Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA;10. Department of Pharmacology, Toxicology and Medicine, Virginia Commonwealth University, Richmond, Virginia, VA, USA;11. Merck Research Laboratories, Rahway, NJ, USA;12. Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana‐Farber Cancer Institute, Boston, MA, USA;13. Centre for Cancer Biology, University of South Australia, Adelaide, SA, Australia;14. Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA;15. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA;16. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA;17. Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France;18. INSERM, U1138, Paris, France;19. Gustave Roussy Cancer Campus, Villejuif, France;20. Department of Genetics, Trinity College, The Smurfit Institute, Dublin, Ireland;21. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria;22. Department of Biology, University of Rome Tor Vergata, Rome, Italy;23. National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy;24. Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK;25. Institute of Pharmacology, University of Bern, Bern, Switzerland;26. Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;27. Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA;28. Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University of Madrid, Madrid, Spain;29. Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain
Abstract:Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.
Keywords:adaptive stress responses  Beclin 1  inflammation  KRAS  mitophagy
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