The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
p53 regulates epithelial–mesenchymal transition and stem cell properties through modulating miRNAs
Open accessAbstract
The epithelial–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.
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Cites
A Third-Generation Lentivirus Vector with a Conditional Packaging System
Dull, T., Zufferey, R., Kelly, M., Mandel, R. J., Nguyen, M., Trono, D., & Naldini, L. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8463-8471.1998 · Cited by 3,341
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
Polyak, K., & Weinberg, R. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2620 · Cited by 3,302
TGF-β1–induced expression of human Mdm2 correlates with late-stage metastatic breast cancer
Araki, S., Eitel, J. A., Batuello, C. N., Bijangi-Vishehsaraei, K., Xie, X.-J., Danielpour, D., Pollok, K. E., Boothman, D. A., & Mayo, L. D. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39194 · Cited by 133
Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
Regulatory networks defining EMT during cancer initiation and progression
Craene, B. D., & Berx, G. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3447 · Cited by 2,487
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
The epigenetics of epithelial-mesenchymal plasticity in cancer
Tam, W. L., & Weinberg, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3336 · Cited by 1,163
Lujambio, A., & Lowe, S. W. (2012) · Nature · doi:10.1038/nature10888 · Cited by 1,084
Metadata
- Authors
- 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.
- Venue
- Nature Cell Biology
- Published
- 2011-02-20
- Volume
- 13
- Issue
- 3
- Pages
- 317-323
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2066441178
- Cited by
- 745
- References
- 3
- FWCI
- 34.61
- Type
- journal article
- Language
- en
- Open access
- green
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- 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. https://doi.org/10.1038/ncb2173
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