Patricia Scott

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the U.S. Identification of CRC driver genes that play a causal role in CRC tumorigenesis and their biochemical pathways has the potential to elucidate the biological processes driving CRC progression, including metastasis, and to identify new prognostic and predictive biomarkers and therapeutic targets. These researchers and their collaborators recently found that the functionally related ion channel genes KCNQ1 and CFTR are tumor suppressor genes whose low expression is associated with poor outcomes in both early stage and metastatic colorectal cancer. KCNQ1 and CFTR were first identified as candidate CRC driver genes in a Sleeping Beauty transposon-mediated forward genetic screen in mice. In follow-up studies, targeted deletion of Kcnq1 in the Apc^Min mouse model of intestinal tumorigenesis resulted in significantly more intestinal tumors. Further, the researchers have found elevated expression of KCNQ1 and CFTR are associated with improved survival in human colorectal cancer. Accordingly, their goal is to determine if KCNQ1 and CFTR can be used clinically as a biomarkers or therapeutic targets. To this end they are using mouse models and 3D organoid cultures generated from mouse and human intestines to determine the mechanisms of tumor suppression by KCNQ1 and CFTR.