Luc Sabourin, PhD

lsabourin@ohri.ca

Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute

Assistant Professor, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa

Research Interests

Cancer progression from a localized neoplastic lesion to an invasive phenotype involves genetic changes resulting in the activation of several genes implicated in proliferation and cell invasion. Cancer cell invasion through basement membranes, into the lymphatics or the blood vessels, relies heavily on the cell's migration machinery and signaling systems. Extensive literature indicate that migration pathways and actin regulators play a crucial role in transformation and are likely to be the mediators of the migratory and invasive phenotype. Our lab is studying the role of the Ste20-like kinase SLK in the control of cell motility. We are investigating the regulation of SLK downstream of migration signaling and characterizing SLK downstream signaling systems. Various approaches such as proteomics, gene knock-outs and transgenics, molecular biology and biochemistry are used to understand SLK signaling.

Several studies have provided direct evidence supporting a role for erbB-2 and c-Met in mammary tumorigenesis. Despite the importance of HER2/Neu/ErbB2 and c-Met in the etiology of breast carcinomas, the molecular mechanisms by which they confer an invasive phenotype is still unclear. Our research efforts are also focused on understanding how growth factor receptors such as ErbB-2 (overexpressed in 25-30% of human breast cancers) and c-Met are coupled to the migration machinery using transgenic models and cell culture systems. We believe that delineating the molecular mechanisms translating growth factor signals to the migration machinery is key in the development of additional therapies targeted at the invasive potential of these tumors.

Selected Publications

L.A. Sabourin, P. Seale, K. Tamai, J. Wagner and M.A. Rudnicki (2000). Caspase-3 cleavage of the Ste20-related kinase SLK releases and activates an apoptosis-inducing kinase domain and an actin disassembling region. Mol Cel Biol, 20:684-696.

S. Wagner, T.A. Flood, P. O'Reilly, K. Hume and L.A. Sabourin (2002). Association of the Ste20-like Kinase SLK with the Microtubule: Role in Rac1-Mediated Regulation of Actin Dynamics during Cell Adhesion and Spreading. J Biol Chem 277: 37685-92.

P. O'Reilly, D. J. Franks, R. Braun and L.A. Sabourin (2005). The Ste20-like kinase SLK is required for cell cycle progression through G2/M. J Biol Chem. 280(51):42383-90.

Z. Chaar, P. O'Reilly, K. Hume and L.A. Sabourin (2006). v-src-Dependent Downregulation of the Ste20-like Kinase SLK by Casein KinaseII. J Biol Chem, 281(38):28193-28199.