Objective Cancer progression, characterized by uncontrolled proliferation and motility of cells, is a complex and deadly process. Integrins, a major cell surface adhesion receptor family, are transmembrane proteins known to regulate cell behaviour by transducing extracellular signals to cytoplasmic protein complexes. We and others have shown that recruitment of specific protein complexes by the cytoplasmic domains of integrins is important in tumorigenesis. Here our aim is to study three interrelated processes in cancer progression which involve integrin signalling, but which have not been elucidated earlier at all. 1) Integrins in cell division (cytokinesis). Since coordinated action of the cytoskeleton and membranes is needed both for cell division and motility, shared integrin functions can regulate both events. 2) Dynamic integrin signalosomes at the leading edge of invading cells. Spatially and temporally regulated, integrin-protein complexes at the front of infiltrating cells are likely to dictate the movement of cancer cells in tissues. 3) Transmembrane segments of integrins as scaffolds for integrin signalling. In addition to cytosolic proteins, integrins most likely interact with proteins within the membrane resulting into new signalling modalities. In this proposal we will use innovative, modern and even unconventional techniques (such as RNAi and live-cell arrays detecting integrin traffic, cell motility and multiplication, laser-microdissection, proteomics and bacterial-two-hybrid screens) to unravel these new integrin functions, for which we have preliminary evidence. Each project will give fundamentally novel mechanistic insight into the role of integrins in cancer. Moreover, these interdisciplinary new openings will increase our understanding in cancer progression in general and will open new possibilities for therapeutic intervention targeting both cancer proliferation and dissemination in the body. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncology Keywords cancer cytokinesis integrin invasion matrix membrane traffic Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2007-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution TEKNOLOGIAN TUTKIMUSKESKUS VTT EU contribution € 737 640,00 Address TEKNIIKANTIE 4 A 02044 VTT ESPOO Finland See on map Activity type Research Organisations Administrative Contact Jaana Heino (Ms.) Principal investigator Johanna Ivaska (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all TEKNOLOGIAN TUTKIMUSKESKUS VTT Finland EU contribution € 737 640,00 Address TEKNIIKANTIE 4 A 02044 VTT ESPOO See on map Activity type Research Organisations Administrative Contact Jaana Heino (Ms.) Principal investigator Johanna Ivaska (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data TURUN YLIOPISTO Finland EU contribution € 791 729,00 Address YLIOPISTONMAKI 20014 Turku See on map Region Manner-Suomi Etelä-Suomi Varsinais-Suomi Activity type Higher or Secondary Education Establishments Administrative Contact Eliisa Särkilahti (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data