RT Journal Article SR Electronic T1 p53 and MicroRNA-34 Are Suppressors of Canonical Wnt Signaling JF Science Signaling JO Sci. Signal. FD American Association for the Advancement of Science SP ra71 OP ra71 DO 10.1126/scisignal.2001744 VO 4 IS 197 A1 Kim, Nam Hee A1 Kim, Hyun Sil A1 Kim, Nam-Gyun A1 Lee, Inhan A1 Choi, Hyung-Seok A1 Li, Xiao-Yan A1 Kang, Shi Eun A1 Cha, So Young A1 Ryu, Joo Kyung A1 Na, Jung Min A1 Park, Changbum A1 Kim, Kunhong A1 Lee, Sanghyuk A1 Gumbiner, Barry M. A1 Yook, Jong In A1 Weiss, Stephen J. YR 2011 UL http://stke.sciencemag.org/content/4/197/ra71.abstract AB Although loss of p53 function and activation of canonical Wnt signaling cascades are frequently coupled in cancer, the links between these two pathways remain unclear. We report that p53 transactivated microRNA-34 (miR-34), which consequently suppressed the transcriptional activity of β-catenin–T cell factor and lymphoid enhancer factor (TCF/LEF) complexes by targeting the untranslated regions (UTRs) of a set of conserved targets in a network of genes encoding elements of the Wnt pathway. Loss of p53 function increased canonical Wnt signaling by alleviating miR-34–specific interactions with target UTRs, and miR-34 depletion relieved p53-mediated Wnt repression. Gene expression signatures reflecting the status of β-catenin–TCF/LEF transcriptional activity in breast cancer and pediatric neuroblastoma patients were correlated with p53 and miR-34 functional status. Loss of p53 or miR-34 contributed to neoplastic progression by triggering the Wnt-dependent, tissue-invasive activity of colorectal cancer cells. Further, during development, miR-34 interactions with the β-catenin UTR affected Xenopus body axis polarity and the expression of Wnt-dependent patterning genes. These data provide insight into the mechanisms by which a p53–miR-34 network restrains canonical Wnt signaling cascades in developing organisms and human cancer.