Matriptase Mediated C-Met Signaling In Breast Cancer

MATRIPTASE MEDIATED c-MET SIGNALING IN BREAST CANCERbyGINA ZORATTIMay 2014Advisor: Dr. Karin ListMajor: Cancer BiologyDegree: Doctor of PhilosophyHistorically proteases have been associated with tumor progression andmetastasis through degradation of the basement membrane. However, in recent yearsthese enzymes have also been shown to play key roles in the activation of growthfactors and cytokines, thereby activating pro-oncogenic signaling pathways. Matriptase(MT-SP1, ST14) is an epithelia-specific pericellular protease which has receivedconsiderable attention in recent years spurred by the consistent dysregulation of theprotease in human epithelial tumors including breast cancer. We have performed bothfunctional and mechanistic studies of matriptase in breast cancer using parallel,complementary in vitro and in vivo genetic “loss-of-function” strategies. To determinethe contribution of matriptase to breast cancer in vivo we used matriptase hypomorhicmice with very low matriptase expression in the mammary gland. When crossed intothe mammary tumor virus (MMTV) Polyomavirus middle T (PymT) mouse geneticmammary tumor model, matriptase hypomorphic mice displayed a significant decreasein tumor burden.