Grant: Project Grant

A protein called beta-catenin is often dysregulated human diseases, most notably in a variety of solid tumors, including colorectal cancer. It was indeed found to be highly express and hyperactive in tissue specimens and cells derived from colorectal cancer and it is viewed as a very promising target for future therapies. However, inhibition of beta-catenin is not trivial as the protein has no enzymatic function. Drug discovery efforts have focused so far on the identification of small molecule inhibitors of the interaction between beta-catenin and other proteins with oncogenic properties, with marginal success. An alternative therapeutic approach would be to promote the degradation of beta-catenin in cancer cells. With this in mind, we have identified an enzyme called USP17, which act as a major regulator of beta-catenin protein levels and growth in colorectal cancer cells. The objective of this research proposal is to define the role of USP17 in the formation and malignant progression of colorectal cancer using in vitro cell culture systems and mouse models.