Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 1 November 2011
Vol. 4, Issue 197, p. ra71
[DOI: 10.1126/scisignal.2001744]

RESEARCH ARTICLES

Editor's Summary

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 p53’s 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).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio.
K. Soni, A. Choudhary, A. Patowary, A. R. Singh, S. Bhatia, S. Sivasubbu, S. Chandrasekaran, and B. Pillai (2013)
Nucleic Acids Res. 41, 4470-4480
   Abstract »    Full Text »    PDF »
Axonal Translation of {beta}-Catenin Regulates Synaptic Vesicle Dynamics.
A. M. Taylor, J. Wu, H.-C. Tai, and E. M. Schuman (2013)
J. Neurosci. 33, 5584-5589
   Abstract »    Full Text »    PDF »
Oncogenic Wnt/{beta}-catenin signalling pathways in the cancer-resistant epididymis have implications for cancer research.
K. Wang, N. Li, C. H. Yeung, J. Y. Li, H. Y. Wang, and T. G. Cooper (2013)
Mol. Hum. Reprod. 19, 57-71
   Abstract »    Full Text »    PDF »
Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and {beta}-Catenin Predicts Distant Metastasis of Colon Cancer.
H. Siemens, J. Neumann, R. Jackstadt, U. Mansmann, D. Horst, T. Kirchner, and H. Hermeking (2013)
Clin. Cancer Res. 19, 710-720
   Abstract »    Full Text »    PDF »
Canonical Wnt signaling regulates Slug activity and links epithelial-mesenchymal transition with epigenetic Breast Cancer 1, Early Onset (BRCA1) repression.
Z.-Q. Wu, X.-Y. Li, C. Y. Hu, M. Ford, C. G. Kleer, and S. J. Weiss (2012)
PNAS 109, 16654-16659
   Abstract »    Full Text »    PDF »
Transcriptional and Post-transcriptional Regulation in TGF-{beta}-mediated epithelial-mesenchymal transition.
M. Saitoh and K. Miyazawa (2012)
J. Biochem. 151, 563-571
   Abstract »    Full Text »    PDF »
miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2.
J. Wei, Y. Shi, L. Zheng, B. Zhou, H. Inose, J. Wang, X. E. Guo, R. Grosschedl, and G. Karsenty (2012)
J. Cell Biol. 197, 509-521
   Abstract »    Full Text »    PDF »
Snail1 controls epithelial-mesenchymal lineage commitment in focal adhesion kinase-null embryonic cells.
X.-Y. Li, X. Zhou, R. G. Rowe, Y. Hu, D. D. Schlaepfer, D. Ilic, G. Dressler, A. Park, J.-L. Guan, and S. J. Weiss (2011)
J. Cell Biol. 195, 729-738
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882