tailieunhanh - Báo cáo khoa học: Apoptosis and autophagy: Targeting autophagy signalling in cancer cells – ‘trick or treats’?

Macroautophagy (hereafter referred to as autophagy) is a tightly regulated lysosome-dependent catabolic pathway. During this process, cytosolic con-stituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes, where their contents are degraded. | MINIREVIEW Apoptosis and autophagy Targeting autophagy signalling in cancer cells - trick or treats Elisabeth A. Corcelle Pietri Puustinen and Marja Jaattela Apoptosis Department and Centre for Genotoxic Stress Research Institute of Cancer Biology Danish Cancer Society Copenhagen Denmark Keywords autophagy cancer kinases phosphatases signalling therapy Correspondence M. UỄỈỂittelỄs Department of Apoptosis Institute of Cancer Biology Danish Cancer Society Strandboulevarden 49 DK-2100 Copenhagen Denmark Fax 45 35257721 Tel 45 35257318 E-mail mj@ Received 23 March 2009 revised 9 July 2009 accepted 24 July 09 doi 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. Introduction Macroautophagy hereafter referred to as autophagy is an evolutionarily conserved lysosomal self-digestion process responsible for the turnover of whole organelles and macromolecules 1 2 . In addition to important housekeeping functions autophagy promotes the survival of starved and stressed

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