Kathleen Goss, Ph.D.

The APC tumor suppressor and Wnt/b-catenin signaling:  critical regulators of development and neoplasia of the intestine and mammary gland

Research Summary

Components of the Wnt/b-catenin pathway, including the APC tumor suppressor, are implicated in both human cancer and tumorigenesis in rodent models in the intestine and breast, among other tissues.  However, the precise molecular actions of APC and Wnt/b-catenin signaling in homeostasis of normal epithelial cells and in tumor initiation and progression remain unknown.  Using both in vivo and in vitro approaches, our work aims to identify 1) the mechanism by which APC acts as a tumor suppressor in epithelial cells; 2) how APC loss promotes breast tumor initiation and progression; and 3) the contribution of Wnt/b-catenin signaling to specific subtypes of cancer.   In the long term, our studies will contribute to the overall understanding of the APC/b-catenin pathway in tissue development and tumorigenesis and perhaps facilitate the design of novel therapeutic approaches to target this pathway in human cancers.

Selected Papers

Heppner Goss, K., Trzpacz, C., Tuohy, T.M.F. and Groden, J. (2002) Attenuated APC alleles produce functional protein from internal translational initiation. Proc. Natl. Acad. Sci. USA. 99, 8161-8166.

Goss, K.H., Risinger, M., Kordich, J., Sanz, M.M., Straughen, J.E., Slovek, L.E., Capobianco, A.J., German, J., Boivin, G.P. and Groden, J. (2002)  Enhanced tumor formation in mice heterozygous for Blm mutation. Science. 297, 2051-2053.

Reichling, T.D., Goss, K.H., Carson, D.J., Ley-Ebert, C., Witte, D., Aronow, B. and Groden, J. (2005) Transcriptional profiles of intestinal tumors in ApcMin/+ mice are unique from those of embryonic intestine and identify novel gene targets dysregulated in human colorectal tumors.  Cancer Res. 65, 166-176.

Mak, G.Z., Kavanaugh, G.M., Buschmann, M.M., Stickley, S.M., Koch, M., Goss, K.H., Waechter, H., Zuk, A. and Matlin, K.S. (2006) Regulated synthesis and functions of Laminin 5 in polarized Madin-Darby Canine Kidney (MDCK) epithelial cells. Mol. Biol. Cell 17, 3664-3677.

Prosperi, J.R., Becher, K.R., Willson, T.A., Collins, M.H., Witte, D.P. and Goss, K.H. (2009)  The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland.  J. Cell Phys. 220, 319-331.

Meyer, S.E., Waltz, S.E. and Goss, K.H. (2009)  The Ron receptor tyrosine kinase is not required for adenoma formation in ApcMin/+ mice. Mol. Carcinogenesis, May 18 (Epub ahead of print).