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Apoptosis and autophagy: Targeting autophagy signalling in cancer cells -'trick or treats'?

Journal

FEBS JOURNAL
Volume 276, Issue 21, Pages 6084-6096

Publisher

WILEY
DOI: 10.1111/j.1742-4658.2009.07332.x

Keywords

autophagy; cancer; kinases; phosphatases; signalling; therapy

Funding

  1. Danish Cancer Society
  2. Danish Medical Research Council
  3. Danish National Research Foundation
  4. European Commission FP7 APO-SYS network
  5. Alfred Benzon Foundation
  6. Meyer Foundation and the Novo Nordisk Foundation

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Macroautophagy (hereafter referred to as autophagy) is a tightly regulated lysosome-dependent catabolic pathway. During this process, cytosolic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes, where their contents are degraded. Autophagy contributes to the maintenance of the cellular energy homeostasis, to the clearance of damaged organelles and to adaptation to environmental stresses. Accordingly, autophagy defects have been linked to a wide range of human pathologies, including cancer. The recent discovery of several evolutionarily conserved genes involved in autophagosome formation has greatly stimulated the autophagy research, and the complex signalling networks regulating mammalian autophagy have begun to emerge. Here, we draw the current picture of signalling pathways connecting mitogenic and stress-induced signals to the initiation and maturation of autophagosomes and discuss the possibilities of their targeting as therapeutic adjuvants in anticancer therapy.

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