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How a lipid mediates tumour suppression. Delivered on 29 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden
Author(s) -
Stenmark Harald
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07900.x
Subject(s) - microbiology and biotechnology , cytokinesis , pi3k/akt/mtor pathway , autophagy , phosphatidylinositol , cancer cell , effector , cell growth , biology , endosome , kinase , chemistry , cell division , cell , signal transduction , cancer , apoptosis , biochemistry , intracellular , genetics
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. PtdIns(3,4,5) P 3 , 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 PtdIns3 P , 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 have revealed two additional functions of PtdIns3 P that might contribute to its tumour suppressor activity. The first involves endosomal sorting and lysosomal downregulation of mitogenic receptors. The second involves regulation of cytokinesis, which is the final stage of cell division. Further elucidation of the mechanisms of tumour suppression mediated by class III PI3K and PtdIns3 P will identify novel Achilles’ heels of the cell’s defence against tumourigenesis and will be useful in the search for prognostic and diagnostic biomarkers in cancer.