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Ambra1 at the crossroad between autophagy and cell death

Oncogene volume 32, pages 3311–3318 (2013)Cite this article

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Abstract

Autophagy is a self-digesting mechanism responsible for the degradation and recycling of most intracellular macromolecules and the removal of damaged organelles by the lysosome. An impressive number of recent studies have provided key information about the regulation of autophagy and its role in cell survival during nutrient depletion and many other stressful situations. In particular, many evidences have highlighted a crucial role of dysregulated autophagy in oncogenesis. Perturbations of the autophagic pathway have been shown to contribute to tumor development. Moreover, cancer cells have developed several mechanisms that allow them to evade chemotherapy-induced cell death, as well as to use autophagy-associated pathways, to potentiate their survival. In this regard, a complex crosstalk between autophagy and apoptosis has recently emerged; the understanding of the molecular mechanisms regulating this interplay may provide new hints on how to properly modulate these processes to halt cancer. Indeed, key proteins originally thought to be apoptosis-specific inhibitors also block autophagy, while apoptosis proteolytic enzymes hamper autophagy by cleaving autophagy-specific proteins and, in some cases, converting them into proapoptotic factors. This review is focused on the role that Ambra1, a central component of the autophagosome formation machinery, has in the switch between autophagy and apoptosis and its implication in cancer development and chemotherapy resistance.

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Acknowledgements

This work was supported by grants from the Italian Ministry of University FIRB, Compagnia di San Paolo to MP, the Ministry of Health of Italy ‘Ricerca Corrente’ and ‘Ricerca Finalizzata’ to MP and GMF, AIRC to MP and MC, and Telethon to GMF. The support of the EU grant ‘Transpath ‘ Marie Curie project to MP is also acknowledged.

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  1. Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy

    G M Fimia, M Corazzari, M Antonioli & M Piacentini

  2. Department of Biology, University of Rome ‘Tor Vergata’, Rome, Italy

    M Corazzari & M Piacentini

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  1. G M Fimia
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Correspondence to M Piacentini.

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Fimia, G., Corazzari, M., Antonioli, M. et al. Ambra1 at the crossroad between autophagy and cell death. Oncogene 32, 3311–3318 (2013). https://doi.org/10.1038/onc.2012.455

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