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Article: The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
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TitleThe polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
 
AuthorsSong, LB1
Li, J5
Liao, WT1
Feng, Y1
Yu, CP1
Hu, LJ1
Kong, QL1
Xu, LH1
Zhang, X1
Liu, WL1
Li, MZ1
Zhang, L1
Kang, TB1
Fu, LW1
Huang, WL1
Xia, YF1
Tsao, SW2
Li, M5
Band, V4
Band, H4
Shi, QH3
Zeng, YX1
Zeng, MS1
 
Issue Date2009
 
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
 
CitationJournal Of Clinical Investigation, 2009, v. 119 n. 12, p. 3626-3636 [How to Cite?]
DOI: http://dx.doi.org/10.1172/JCI39374
 
AbstractThe 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 epithelialmesenchymal 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-3β 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.
 
ISSN0021-9738
2013 Impact Factor: 13.765
2013 SCImago Journal Rankings: 9.511
 
DOIhttp://dx.doi.org/10.1172/JCI39374
 
PubMed Central IDPMC2786794
 
ISI Accession Number IDWOS:000272386400013
Funding AgencyGrant Number
National Natural Science Foundation of China30630068
30670803
30770836
30872931
Ministry of Science and Technology of China2007AA02Z477
2006DA102A11
2006AA02Z4B4
Research Grant Council (Hong Kong)HKU7770/07M
777809
Funding Information:

We thank Xin Lin and Peng Huang (University of Texas M.D. Anderson Cancer Center, Houston,Texas, USA) for their valuable comments and extensive editing of the manuscript. This study was supported by grants from the National Natural Science Foundation of China (30630068,30670803,30770836, and 30872931) as well as grants from the Ministry of Science and Technology of China (2007AA02Z477, 2006DA102A11, and 2006AA02Z4B4). We thank the support from the Research Grant Council (Hong Kong) for this project (grants HKU7770/07M and 777809, to S.W. Tsao and M.-S. Zeng).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSong, LB
 
dc.contributor.authorLi, J
 
dc.contributor.authorLiao, WT
 
dc.contributor.authorFeng, Y
 
dc.contributor.authorYu, CP
 
dc.contributor.authorHu, LJ
 
dc.contributor.authorKong, QL
 
dc.contributor.authorXu, LH
 
dc.contributor.authorZhang, X
 
dc.contributor.authorLiu, WL
 
dc.contributor.authorLi, MZ
 
dc.contributor.authorZhang, L
 
dc.contributor.authorKang, TB
 
dc.contributor.authorFu, LW
 
dc.contributor.authorHuang, WL
 
dc.contributor.authorXia, YF
 
dc.contributor.authorTsao, SW
 
dc.contributor.authorLi, M
 
dc.contributor.authorBand, V
 
dc.contributor.authorBand, H
 
dc.contributor.authorShi, QH
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorZeng, MS
 
dc.date.accessioned2010-10-31T10:37:47Z
 
dc.date.available2010-10-31T10:37:47Z
 
dc.date.issued2009
 
dc.description.abstractThe 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 epithelialmesenchymal 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-3β 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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationJournal Of Clinical Investigation, 2009, v. 119 n. 12, p. 3626-3636 [How to Cite?]
DOI: http://dx.doi.org/10.1172/JCI39374
 
dc.identifier.doihttp://dx.doi.org/10.1172/JCI39374
 
dc.identifier.epage3636
 
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dc.identifier.isiWOS:000272386400013
Funding AgencyGrant Number
National Natural Science Foundation of China30630068
30670803
30770836
30872931
Ministry of Science and Technology of China2007AA02Z477
2006DA102A11
2006AA02Z4B4
Research Grant Council (Hong Kong)HKU7770/07M
777809
Funding Information:

We thank Xin Lin and Peng Huang (University of Texas M.D. Anderson Cancer Center, Houston,Texas, USA) for their valuable comments and extensive editing of the manuscript. This study was supported by grants from the National Natural Science Foundation of China (30630068,30670803,30770836, and 30872931) as well as grants from the Ministry of Science and Technology of China (2007AA02Z477, 2006DA102A11, and 2006AA02Z4B4). We thank the support from the Research Grant Council (Hong Kong) for this project (grants HKU7770/07M and 777809, to S.W. Tsao and M.-S. Zeng).

 
dc.identifier.issn0021-9738
2013 Impact Factor: 13.765
2013 SCImago Journal Rankings: 9.511
 
dc.identifier.issue12
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2786794
 
dc.identifier.pmid19884659
 
dc.identifier.scopuseid_2-s2.0-72849130207
 
dc.identifier.spage3626
 
dc.identifier.urihttp://hdl.handle.net/10722/124498
 
dc.identifier.volume119
 
dc.languageeng
 
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Clinical Investigation
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshNasopharynx - cytology - metabolism
 
dc.subject.meshNuclear Proteins - antagonists and inhibitors - genetics - metabolism
 
dc.subject.meshPTEN Phosphohydrolase - genetics - metabolism
 
dc.subject.meshProto-Oncogene Proteins - antagonists and inhibitors - genetics - metabolism
 
dc.subject.meshRepressor Proteins - antagonists and inhibitors - genetics - metabolism
 
dc.titleThe polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
 
dc.typeArticle
 
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Author Affiliations
  1. Sun Yat-Sen University Cancer Center
  2. The University of Hong Kong
  3. University of Science and Technology of China
  4. University of Nebraska Medical Center
  5. Sun Yat-Sen University