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Sci. Signal., 1 November 2011
Vol. 4, Issue 197, p. ra71
p53 Activates MicroRNA-34 to Inhibit Wnt Signaling
The tumor suppressor p53 is missing or nonfunctional in many cancers, whereas the canonical Wnt signaling pathway is frequently activated. Here, Kim et al. show that p53 restrained Wnt signaling during Xenopus development, whereas loss of p53 function led to aberrant activation of the canonical Wnt signaling pathway, with microRNA-34 (miR-34) providing the connection between the two. They found that p53 stimulated production of miR-34, which, in turn, targeted key genes in the Wnt signaling pathway. Analyses of gene expression data sets indicated that loss of p53 or miR-34 function was associated with activation of Wnt signaling in human cancers; moreover, loss of p53 function increased Wnt signaling in colon cancer cells in vitro. In p53-mutant colon cancer cells, miR-34 attenuated Wnt signaling and decreased the invasiveness of these cells in vitro. Thus, the p53–miR-34–Wnt pathway appears to be crucial not only during development but also for p53s tumor suppressor function.
Citation: 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, S. Lee, B. M. Gumbiner, J. I. Yook, S. J. Weiss, p53 and MicroRNA-34 Are Suppressors of Canonical Wnt Signaling. Sci. Signal.4, ra71 (2011).
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