The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
Open accessAbstract
The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.
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Cited by
Dang, C. V. (2012) · Cell · doi:10.1016/j.cell.2012.03.003 · Cited by 3,390
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
The epigenetics of epithelial-mesenchymal plasticity in cancer
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The functions and regulation of the PTEN tumour suppressor: new modes and prospects
Lee, Y.-R., Chen, M., & Pandolfi, P. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0015-0 · Cited by 917
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Metadata
- Authors
- Song, L.-B., Li, J., Liao, W.-T., Feng, Y., Yu, C.-P., Hu, L.-J., Kong, Q.-L., Xu, L.-H., Zhang, X., Liu, W.-L., Li, M.-Z., Zhang, L., Kang, T.-B., Fu, L.-W., Huang, W.-L., Xia, Y.-F., Tsao, S. W., Li, M., Band, V., Band, H., Shi, Q.-H., Zeng, Y.-X., & Zeng, M.-S.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-12-01
- Volume
- 119
- Issue
- 12
- Pages
- 3626-3636
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2049400611
- Cited by
- 398
- References
- 10
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Open access
- green
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- Song, L.-B., Li, J., Liao, W.-T., Feng, Y., Yu, C.-P., Hu, L.-J., Kong, Q.-L., Xu, L.-H., Zhang, X., Liu, W.-L., Li, M.-Z., Zhang, L., Kang, T.-B., Fu, L.-W., Huang, W.-L., Xia, Y.-F., Tsao, S. W., Li, M., Band, V., . . . Zeng, M.-S. (2009). The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci39374
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