Our research is dedicated to understanding the role of cell surface proteins in cell behavior, in particular how these proteins govern communication between the exterior and the interior of tumor cells.
Molecular activities at interfaces in biological systems are fundamental for life, and disturbances therein can lead to disease. Such molecular interfaces exist between individual molecules, between cells and the extra cellular matrix, or between different organ systems. Our research is directed toward understanding the molecular mechanisms underlying disease, in particular cancer.
Over the past few years, we have focused on ADAMs (a disintegrin and metalloprotease) and in particular the family member ADAM12. This group of multidomain transmembrane proteases play important roles in ectodomain shedding of other cell surface proteins, as well as in cell-cell and cell-matrix interactions.
Our interest in ADAMs include:
• ADAM12´s significance in clinical pathologic diagnosis and prognosis
• ADAM12 and the role of the prodomain and metalloprotease activity
• ADAM12´s interaction with cell surface receptors
• ADAM12 and its cytoplasmic tail
• Identification of novel regulatory mechanisms of ADAM protease activity
Kveiborg M, Jacobsen J, Lee MH, Nagase H, Wewer UM, Murphy G (2010). Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of Metalloproteinases (TIMP)-2. Biochem J. Jun 10. Epub ahead of print
Stautz D, Sanjay A, Hansen MT, Albrechtsen R, Wewer UM, Kveiborg M (2010). ADAM12 localizes with c-Src to actin-rich structures at the cell periphery and regulates Src kinase activity. Exp Cell Res.316:55-67.
Lydolph MC, Morgan-Fisher M, Høye AM, Couchman JR, Wewer UM, Yoneda A (2009). Alpha9beta1 integrin in melanoma cells can signal different adhesion states for migration and anchorage. Exp Cell Res. 315:3312-24.
Kveiborg M, Albrechtsen R, Couchman JR, Wewer UM (2008). Cellular roles of ADAM12 in health and disease. Int J Biochem Cell Biol. 40(9):1685-702.
Jacobsen J, Visse R, Sørensen HP, Enghild JJ, Brew K, Wewer UM, Nagase H (2008). Catalytic properties of ADAM12 and its domain deletion mutants. Biochemistry. 47:537-47
Atfi A, Dumont E, Colland F, Bonnier D, L'helgoualc'h A, Prunier C, Ferrand N, Clément B, Wewer UM, Théret N. (2007). The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor. J Cell Biol. 178:201-8
Fröhlich C, Albrechtsen R, Dyrskjøt L, Rudkjær L, Ørntoft RF, and Wewer UM. (2006). Molecular profiling of ADAM12 in human bladder cancer. Clin Cancer Res. 12:7359-68
Kveiborg M, Fröhlich C, Albrechtsen R, Tischler V, Dietrich N, Holck P, Kronqvist P, Rank F, Mercurio AM, and Wewer UM. (2005). A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res. 65:4754-61