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Báo cáo khoa học: How a lipid mediates tumour suppression Delivered on 29 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden

Phosphorylated derivatives of the membrane lipid phosphatidylinositol (PtdIns), known as phosphoinositides (PIs), regulate membrane-proximal cellular processes by recruiting specific protein effectors involved in cell signalling, membrane trafficking and cytoskeletal dynamics. Two PIs that are generated through the activities of distinct PI 3-kinases (PI3Ks) are of special interest in cancer research. | ỊFEBS Journal THE SIR HANS KREBS LECTURE How a lipid mediates tumour suppression Delivered on 29 June 2010 at the 35th FEBS Congress in Gothenburg Sweden Harald Stenmark1 2 1 Centre for Cancer Biomedicine Faculty of Medicine University of Oslo Norway 2 Institute for Cancer Research the Norwegian Radium Hospital Oslo University Hospital Montebello Norway Keywords autophagy cancer cell division cytokinesis endocytosis PI 3-kinase tumour suppressor Correspondence H. Stenmark Institute for Cancer Research the Norwegian Radium Hospital Montebello N-0310 Oslo Norway Fax 47 22781845 Tel 47 22781818 E-mail stenmark@ulrik.uio.no Re-use of this article is permitted in accordance with the Terms and Conditions set out at http wileyonlinelibrary.com onlineopen OnlineOpen_Terms Received 27 July 2010 revised 12 September 2010 accepted 4 October 2010 doi 10.1111 j.1742-4658.2010.07900.x Phosphorylated derivatives of the membrane lipid phosphatidylinositol PtdIns known as phosphoinositides Pls regulate membrane-proximal cellular processes by recruiting specific protein effectors involved in cell signalling membrane trafficking and cytoskeletal dynamics. Two PIs that are generated through the activities of distinct PI 3-kinases PI3Ks are of special interest in cancer research. PtdIns 3 4 5 P3 generated by class I PI3Ks functions as tumour promotor by recruiting effectors involved in cell survival proliferation growth and motility. Conversely there is evidence that PtdIns3P generated by class III PI3K functions in tumour suppression. Three subunits of the class III PI3K complex Beclin 1 UVRAG and BIF-1 have been independently identified as tumour suppressors in mice and humans and their mechanism of action in this context has been proposed to entail activation of autophagy a catabolic pathway that is considered to mediate tumour suppression by scavenging damaged organelles that would otherwise cause DNA instability through the production of reactive oxygen species. Recent studies .