Therapies for Cancer
Controlling tumor metastasis through enhancement of cadherin function
Cadherin-mediated cell adhesion is a dynamic and tightly regulated process with important implications for development, morphogenesis, and disease. The Gumbiner lab is gaining an understanding of the basic mechanisms of cadherin function and applying this knowledge to disease states associated with deficits in cadherin function. Dr. Gumbiner has shown that cadherins can be physiologically regulated by changes in conformation and/or physical state at the cell surface independent of internalization or catenin dissociation, other mechanisms that have been proposed to control cadherins.
Loss of E-cadherin expression is a common finding in cancer and is strongly associated with tumor metastasis. However, many metastases still express E-cadherin and E-cadherin may help clusters of tumor cells become invasive. Dr. Gumbiner hypothesizes that the E-cadherin in these tumors exists in a dynamic state that allows cells to remodel their adhesions and migrate. Indeed, he has found that activating cadherin in experimental cancer models showed reduced metastasis.
These findings support the idea that inactive cadherin present on tumor cells allows for cell metastasis. Consequently, in addition to evaluating expression levels, it may be important to assess the activity state of cell surface cadherin. Use of cadherin activating compounds may represent a novel therapeutic approach to prevent metastasis when used as an adjunct therapy for E-cadherin-positive tumors. Dr. Gumbiner would be interested in industry collaborations to facilitate further testing and validation of potentially therapeutic compounds in various models of disease, including cancer metastasis, inflammatory vascular disease, and endothelial dysfunction.
Stage of Development
- Pre-clinical in vitro
- Pre-clinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Petrova, Y.I., M.M. Spano, and B.M. Gumbiner, (2012) Conformational epitopes at cadherin calcium- binding sites and p120-catenin phosphorylation regulate cell adhesion. Molec. Biol. Cell. 23:2092-2108. PMCID: PMC3364174
- Kim, N.G., Koh, E.J., and Gumbiner, B.M. (2011) E-cadherin mediates contact inhibition of cell proliferation through Hippo signaling pathway components. Proc. Natl. Acad. Sci.., 108: 11930-11935. PMCID: PMC3141988
- Petrova, Y.I., Schecterson, L., and Gumbiner, B.M. (2016) Roles for E-cadherin cell surface regulation in cancer. Mol. Biol. Cell, 27(21):3233-3244; doi:10.1091/mbc.E16-01-005, PMCID: PMC5170857