p53 and mMicroRNA-34 are suppressors of canonical Wnt signaling

Cited 249 time in scopus
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Title
p53 and mMicroRNA-34 are suppressors of canonical Wnt signaling
Author(s)
N H Kim; H S Kim; N G Kim; I Lee; H S Choi; X Y Li; S E Kang; S Y Cha; J K Ryu; J M Na; C Park; K Kim; Sanghyuk Lee; B M Gumbiner; J I Yook; S J Weiss
Bibliographic Citation
Science Signaling, vol. 4, no. 197, pp. ra71-ra71
Publication Year
2011
Abstract
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.
ISSN
1937-9145
Publisher
Amer Assoc Advancement Science
DOI
http://dx.doi.org/10.1126/scisignal.2001744
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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