HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin

beta-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of beta-catenin is a critical step for expressing target genes. beta-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/beta-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the beta-catenin protein in the cytoplasm. Thus, Wnt/beta-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic beta-catenin functions related to HuR-mediated RNA metabolism in cancer cells. (C) 2014 Elsevier Inc. All rights reserved.