Identification of ß-catenin dependent and independent genes in an orthotopic model of pancreatic cancer

Wnt signaling regulates metazoan development and homeostasis, in part by ß-catenin dependent activation and repression of a large number of genes. However, Wnt signaling also regulates genes independent of ß-catenin, genes that are less well characterized. In this study, using a pan-Wnt inhibitor we performed a comprehensive transcriptome analysis in a Wnt-addicted orthotopic cancer model to delineate the ß-catenin-dependent and independent arms of Wnt signaling. We find that while a large percentage of Wnt-regulated genes are regulated by ß-catenin, ten percent of these genes are regulated independent of ß-catenin. Interestingly, a large proportion of these ß-catenin independent genes are Wnt-repressed. Overall design: Timecourse RNA-seq in HPAF-II cells treated with ETC-159 with or without mutation in ß-catenin