Autophagy in malignant transformation and cancer progression

• Published in: The EMBO journal Vol. 34; no. 7; pp. 856 - 880
• Main Authors: Galluzzi, Lorenzo, Pietrocola, Federico, Bravo-San Pedro, José Manuel, Amaravadi, Ravi K, Baehrecke, Eric H, Cecconi, Francesco, Codogno, Patrice, Debnath, Jayanta, Gewirtz, David A, Karantza, Vassiliki, Kimmelman, Alec, Kumar, Sharad, Levine, Beth, Maiuri, Maria Chiara, Martin, Seamus J, Penninger, Josef, Piacentini, Mauro, Rubinsztein, David C, Simon, Hans-Uwe, Simonsen, Anne, Thorburn, Andrew M, Velasco, Guillermo, Ryan, Kevin M, Kroemer, Guido
• Format: Journal Article
• Language: English
• Published: London Blackwell Publishing Ltd 01.04.2015; Nature Publishing Group UK; Springer Nature B.V; BlackWell Publishing Ltd
• Subjects: adaptive stress responses; Animals; Autophagy; Beclin 1; Cancer therapies; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cellular biology; EMBO03; EMBO07; Environmental stress; Humans; inflammation; KRAS; mitophagy; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Review; Reviews; Tumor Escape; Tumor Suppressor Proteins - immunology; Tumor Suppressor Proteins - metabolism; mitophagy; KRAS; adaptive stress responses; inflammation; Beclin 1
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.15252/embj.201490784

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. Graphical Abstract Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.