Publications

Abstract

The loss of beta-catenin inhibitory components is a well-established mechanism of carcinogenesis but beta-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the beta-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a beta-catenin activator function, depletion of JRK in several cancer cell lines repressed beta-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of beta-catenin target genes and increased cell proliferation. This study shows that JRK is required for beta-catenin hyperactivity regardless of the adenomatous polyposis coli/beta-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.