P53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs

Chun Ju Chang, Chi-Hong Chao, Weiya Xia, Jer Yen Yang, Yan Xiong, Chia Wei Li, Wen Hsuan Yu, Sumaiyah K. Rehman, Jennifer L. Hsu, Heng Huan Lee, Mo Liu, Chun Te Chen, Dihua Yu, Mien Chie Hung*

*Corresponding author for this work

Research output: Contribution to journalArticle

502 Scopus citations

Abstract

The epithelialg-mesenchymal transition (EMT) has recently been linked to stem cell phenotype. However, the molecular mechanism underlying EMT and regulation of stemness remains elusive. Here, using genomic approaches, we show that tumour suppressor p53 has a role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of the microRNA miR-200c. p53 transactivates miR-200c through direct binding to the miR-200c promoter. Loss of p53 in mammary epithelial cells leads to decreased expression of miR-200c and activates the EMT programme, accompanied by an increased mammary stem cell population. Re-expressing miR-200c suppresses genes that mediate EMT and stemness properties and thereby reverts the mesenchymal and stem-cell-like phenotype caused by loss of p53 to a differentiated epithelial cell phenotype. Furthermore, loss of p53 correlates with a decrease in the level of miR-200c, but an increase in the expression of EMT and stemness markers, and development of a high tumour grade in a cohort of breast tumours. This study elucidates a role for p53 in regulating EMT-MET (mesenchymal-epithelial transition) and stemness or differentiation plasticity, and reveals a potential therapeutic implication to suppress EMT-associated cancer stem cells through activation of the p53-miR-200c pathway.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalNature Cell Biology
Volume13
Issue number3
DOIs
StatePublished - 1 Mar 2011

Fingerprint Dive into the research topics of 'P53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs'. Together they form a unique fingerprint.

  • Cite this

    Chang, C. J., Chao, C-H., Xia, W., Yang, J. Y., Xiong, Y., Li, C. W., Yu, W. H., Rehman, S. K., Hsu, J. L., Lee, H. H., Liu, M., Chen, C. T., Yu, D., & Hung, M. C. (2011). P53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nature Cell Biology, 13(3), 317-323. https://doi.org/10.1038/ncb2173