Autophagy and cancer - issues we need to digest

Advance Online Publication May 28, 2012 doi: 10.1242/?jcs.093708 May 15, 2012 J Cell Sci 125, 2349-2358. Emma Y. Liu and Kevin M. Ryan*

Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK ?* Author for correspondence (k.ryan{at}beatson.gla.ac.uk) Autophagy is an evolutionarily conserved catabolic pathway that has multiple roles in carcinogenesis and cancer therapy. It can inhibit the initiation of tumorigenesis through limiting cytoplasmic damage, genomic instability and inflammation, and the loss of certain autophagy genes can lead to cancer. Conversely, autophagy can also assist cells in dealing with stressful metabolic environments, thereby promoting cancer cell survival. In fact, some cancers rely on autophagy to survive and progress. Furthermore, tumour cells can exploit autophagy to cope with the cytotoxicity of certain anticancer drugs. By contrast, it appears that certain therapeutics require autophagy for the effective killing of cancer cells. Despite these dichotomies, it is clear that autophagy has an important, if complex, role in cancer. This is further exemplified by the fact that autophagy is connected with major cancer networks, including those driven by p53, mammalian target of rapamycin (mTOR), RAS and glutamine metabolism. In this Commentary, we highlight recent advances in our understanding of the role that autophagy has in cancer and discuss current strategies for targeting autophagy for therapeutic gain.

Key words This article is part of a Minifocus on Autophagy. For further reading, please see related articles: ‘Ubiquitin-like proteins and autophagy at a glance’ by Tomer Shpilka et al. (J. Cell Sci. 125, 2343-2348) and ‘Autophagy and cell growth – the yin and yang of nutrient responses’ by Thomas Neufeld (J. Cell Sci. 125, 2359-2368).

Funding

Work in the Tumour Cell Death Laboratory is supported by Cancer Research UK and the Association for International Cancer Research.

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Autophagy and cell growth - the yin and yang of nutrient responses

Advance Online Publication May 30, 2012 doi: 10.1242/?jcs.103333 May 15, 2012 J Cell Sci 125, 2359-2368. Thomas P. Neufeld?

Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA neufeld{at}med.umn.edu As a response to nutrient deprivation and other cell stresses, autophagy is often induced in the context of reduced or arrested cell growth. A plethora of signaling molecules and pathways have been shown to have opposing effects on cell growth and autophagy, and results of recent functional screens on a genomic scale support the idea that these processes might represent mutually exclusive cell fates. Understanding the ways in which autophagy and cell growth relate to one another is becoming increasingly important, as new roles for autophagy in tumorigenesis and other growth-related phenomena are uncovered. This Commentary highlights recent findings that link autophagy and cell growth, and explores the mechanisms underlying these connections and their implications for cell physiology and survival. Autophagy and cell growth can inhibit one another through a variety of direct and indirect mechanisms, and can be independently regulated by common signaling pathways. The central role of the mammalian target of rapamycin (mTOR) pathway in regulating both autophagy and cell growth exemplifies one such mechanism. In addition, mTOR-independent signaling and other more direct connections between autophagy and cell growth will also be discussed.

Key words This article is part of a Minifocus on Autophagy. For further reading, please see related articles: ‘Ubiquitin-like proteins and autophagy at a glance’ by Tomer Shpilka et al. (J. Cell Sci. 125, 2343-2348) and ‘Autophagy and cancer – issues we need to digest’ by Emma Liu and Kevin Ryan (J. Cell Sci. 125, 2349-2358).

Funding

The work of our laboratory is supported by the National Institutes of Health [grant number GM62509]. Deposited in PMC for release after 12 months.

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