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Cell Adhesion and Cancer Principal investigator Johanna Ivaska, PhD, Professor of Molecular Cell Biology Turku Centre for Biotechnology, University of Turku, Tykistökatu 6A, 20520 Turku, Finland Tel.: +358 2 333 7954, Fax: +358 2 251 8808 E-mail: [email protected] Research Integrins and receptor tyrosine kinases (RTKs) are cell surface receptors mediating biological functions such as cell survival, proliferation and cell migration. Integrins, through direct binding to extracellular molecules, provide a physical link between the cell cytoskeleton and the surrounding environment and signal by recruiting adaptor and signalling proteins to their cytoplasmic domain. The loss or perturbation of mechanisms that would normally control integrin-mediated cell adhesion or RTK signaling is associated with a number of diseases including cancer metastasis. Our focus is to investigate how integrin traffic, activity and signalling are regulated under normal and pathological conditions. To this effect we have performed genome-wide screens, to identify regulators of integrin traffic and signalling, and drug screens to identify key targets implicated in cancer cell invasion. Links: https://www.btk.fi/research/research-groups/ivaska/ Current topics Dissecting integrin trafficking pathways regulating signaling and migration Investigating SHARPIN-mediated regulation of integrins in tissue morphogenesis and cancer Defining the role of myosin-X and filopodia in cancer cell invasion Investigating novel regulators of integrin activity Integrin-RTK crosstalk Personnel Senior scientists/post docs Antti Arjonen, Maria Georgiadou, Guillaume Jacquemet, Anja Mai, Elisa Närvä, Emilia Peuhu PhD students Jonna Alanko, Nicola De Franceschi, Riina Kaukonen, Johanna Lilja, Pranshu Sahgal, Reetta Virtakoivu Technicians Petra Laasola, Jenni Siivonen, Markku Saari (Microscope Technician) Research support coordinator Hellyeh Hamidi Recent publications (2011-) Rantala JK, Pouwels J, Pellinen T, Veltel S, Laasola P, Mattila E, Potter C, Duffy T, Sundberg JP, Askari JA, Humphries M, Kallioniemi O, Parsons M, Salmi M, Ivaska J. SHARPIN is an endogenous inhibitor of beta1-integrin activation. Nat Cell Biol 13(11):1315-24, 2011. Mai A, Veltel S, Pellinen T, Padzik A, Coffey E, Marjomäki V, Ivaska J. Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor trafficking in migrating cancer cells. J Cell Biol 194(2):291-306, 2011. Pellinen T, Rantala JK, Arjonen A, Mpindi JP, Kallioniemi O, Ivaska J. A functional genetic screen reveals new regulators of beta1-integrin activity. J Cell Sci 125(Pt3):649-61, 2012. Pouwels J, De Franceschi N. Rantakari P, Auvinen K, Karikoski M, Mattila E, Potter C, Sundberg J, Hogg N, Gahmberg CG, Salmi M, Ivaska J. SHARPIN regulates uropod detachment in migrating lymphocytes. Cell Rep 5(3):619-28, 2013. Arjonen A, Kaukonen R, Mattila E, Rouhi P, Högnäs G, Sihto H, Miller BW, Morton JP, Bucher E, Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H, Ivaska J. Mutant p53associated myosin-X upregulation promotes breast cancer invasion and metastasis. J Clin Invest 124(3):1069-108, 2014.