Extracellular proteases can degrade extracellular matrix proteins and reshape the tissue microenvironment as well as cleave and activate signaling molecules such as growth factors and their receptors. These processes are essential for normal physiological tissue development, remodeling, and repair. On the flip side, tissue malfunction and tissue destruction due to dysregulated extracellular proteolysis characterize many pathological conditions including cancer. Extracellular proteolytic processes are critically involved in tumor growth, invasion, and dissemination of cancer cells to other organs. We are particularly interested in a family of cell-surface-anchored proteases: the type II transmembrane serine proteases (TTSPs) and their role in tissue remodeling during epithelial development and carcinogenesis. Understanding the physiological role of extracellular proteases in tissue development and homeostasis is important in order to pinpoint how dysregulated proteolysis can cause or contribute to cancer progression. The motivation behind parallel investigations of normal physiology and pathology is the idea that carcinogenesis often involves pathways, including proteolytic pathways, that are important in normal development and have gone awry in cancer. Generation and characterization of mouse models, including models of human breast and prostate cancer, play an integral role in our research. We use knock-out and transgenic mice for selected extracellular proteases and protease inhibitors as unique tools to identify critical proteolytic pathways in health and disease.
Type II transmembrane serine proteases as potential targets for cancer therapy. Murray AS, Varela FA, List K. Biol Chem. 2016;397:815-26.
Zoratti GL, Tanabe LM, Varela FA, Murray AS, Bergum C, Colombo É, Lang JE, Molinolo AA, Leduc R, Marsault E, Boerner J, List K. Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling. Nat Commun. 2015;6:6776.
Miller GS, Zoratti GL, Murray AS, Bergum C, Tanabe LM, List K. HATL5: A Cell Surface Serine Protease Differentially Expressed in Epithelial Cancers. PLoS One. 2014;9:e87675.
Miller GS, List K. The matriptase-prostasin proteolytic cascade in epithelial development and pathology. Cell Tissue Res. 2013;351:245-53.
Bergum C, Zoratti G, Boerner J, List K. Strong expression association between matriptase and its substrate prostasin in breast cancer. J Cell Physiol. 2012;227:1604-9
Mueller KL, Madden JM, Zoratti GL, Kuperwasser C, List K, Boerner JL. Fibroblast-secreted hepatocyte growth factor mediates epidermal growth factor receptor tyrosine kinase inhibitor resistance in triple-negative breast cancers through paracrine activation of Met. Breast Cancer Res. 2012;14:R104.
Bergum C*, Zoratti G*, Boerner J, List K. Strong expression association between matripase and its substrate prostasin in breast cancer. J Cell Physiol. 2011 Jun 15. doi:10.1002/jcp.22877. *equal contribution
Sales KU, Masedunskas A, Bey AL, Rasmussen AL, Weigert R, List K, Szabo R, Overbeek PA, Bugge TH. Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. Nat Genet. 2010;42:676-83.
Bergum C, List K. Loss of the matriptase inhibitor HAI-2 during prostate cancer progression. Prostate. 2010;70:1422-8.
Education and Training
PhD (2000) University of Copenhagen, Denmark
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7700 Recent Developments in Cancer Biology