Autophagy in malignant transformation and cancer progression

Lorenzo Galluzzi, Federico Pietrocola, José Manuel Bravo-San Pedro, 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 SimonsenAndrew M. Thorburn, Guillermo Velasco, Kevin M. Ryan, Guido Kroemer

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish
Pages (from-to)856-880
Number of pages25
JournalEMBO Journal
Volume34
Issue number7
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Adaptive stress responses
  • Beclin 1
  • inflammation
  • KRAS
  • mitophagy

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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  • Cite this

    Galluzzi, L., Pietrocola, F., Bravo-San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., Kimmelman, A., Kumar, S., Levine, B., Maiuri, M. C., Martin, S. J., Penninger, J., Piacentini, M., Rubinsztein, D. C., Simon, H. U., ... Kroemer, G. (2015). Autophagy in malignant transformation and cancer progression. EMBO Journal, 34(7), 856-880. https://doi.org/10.15252/embj.201490784