• Monday Jan. 9th at 12:00pm: BC Cancer Research Seminar Series presents "CELF1 is a central node in post-transcriptional regulatory programs underlying the epithelial-mesenchymal transition" by Dr. Joel Neilson
The importance of translational regulation in tumor biology is increasingly appreciated. Here, we leverage polyribosomal profiling to prospectively define translational regulatory programs underlying epithelial to mesenchymal transition (EMT) in breast epithelial cells. We identify a group of ten translationally regulated drivers of EMT sharing a common GU-rich cis-element within the 3’ untranslated region (UTR) of their mRNA. These cis-elements, necessary for the regulatory activity imparted by these 3’ UTRs, are directly bound by the CELF1 protein, which itself is regulated post-translationally during the EMT program. CELF1 is necessary and sufficient for both mesenchymal transition and metastatic colonization, and CELF1 protein, but not mRNA, is significantly overexpressed in human breast cancer tissues. Our data present an eleven component genetic pathway, invisible to transcriptional profiling approaches, in which the CELF1 protein functions as a central node controlling translational activation of genes driving EMT and ultimately tumor progression.