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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

TitleThe polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells
Authors
Issue Date2009
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 2009, v. 119 n. 12, p. 3626-3636 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/124498
ISSN
2014 Impact Factor: 13.215
2013 SCImago Journal Rankings: 9.511
PubMed Central ID
ISI Accession Number ID
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).

References

 

DC FieldValueLanguage
dc.contributor.authorSong, LBen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorLiao, WTen_HK
dc.contributor.authorFeng, Yen_HK
dc.contributor.authorYu, CPen_HK
dc.contributor.authorHu, LJen_HK
dc.contributor.authorKong, QLen_HK
dc.contributor.authorXu, LHen_HK
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorLiu, WLen_HK
dc.contributor.authorLi, MZen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorKang, TBen_HK
dc.contributor.authorFu, LWen_HK
dc.contributor.authorHuang, WLen_HK
dc.contributor.authorXia, YFen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorBand, Ven_HK
dc.contributor.authorBand, Hen_HK
dc.contributor.authorShi, QHen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorZeng, MSen_HK
dc.date.accessioned2010-10-31T10:37:47Z-
dc.date.available2010-10-31T10:37:47Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Clinical Investigation, 2009, v. 119 n. 12, p. 3626-3636en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124498-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.relation.ispartofJournal of Clinical Investigationen_HK
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 cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=119&issue=12&spage=3626&epage=3636&date=2009&atitle=The+polycomb+group+protein+Bmi-1+represses+the+tumor+suppressor+PTEN+and+induces+epithelial-mesenchymal+transition+in+human+nasopharyngeal+epithelial+cells-
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI39374en_HK
dc.identifier.pmid19884659en_HK
dc.identifier.pmcidPMC2786794-
dc.identifier.scopuseid_2-s2.0-72849130207en_HK
dc.identifier.hkuros182700en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-72849130207&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume119en_HK
dc.identifier.issue12en_HK
dc.identifier.spage3626en_HK
dc.identifier.epage3636en_HK
dc.identifier.isiWOS:000272386400013-
dc.publisher.placeUnited Statesen_HK
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dc.identifier.scopusauthoridSong, LB=34873620400en_HK
dc.identifier.scopusauthoridLi, J=36066643600en_HK
dc.identifier.scopusauthoridLiao, WT=9746012000en_HK
dc.identifier.scopusauthoridFeng, Y=7404543909en_HK
dc.identifier.scopusauthoridYu, CP=26425333300en_HK
dc.identifier.scopusauthoridHu, LJ=16401449400en_HK
dc.identifier.scopusauthoridKong, QL=35388892800en_HK
dc.identifier.scopusauthoridXu, LH=7404744203en_HK
dc.identifier.scopusauthoridZhang, X=36037212800en_HK
dc.identifier.scopusauthoridLiu, WL=14031879600en_HK
dc.identifier.scopusauthoridLi, MZ=7405262671en_HK
dc.identifier.scopusauthoridZhang, L=35239292600en_HK
dc.identifier.scopusauthoridKang, TB=7402965550en_HK
dc.identifier.scopusauthoridFu, LW=7401812745en_HK
dc.identifier.scopusauthoridHuang, WL=36065549400en_HK
dc.identifier.scopusauthoridXia, YF=7403027273en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridLi, M=7405266040en_HK
dc.identifier.scopusauthoridBand, V=7006194715en_HK
dc.identifier.scopusauthoridBand, H=7005895506en_HK
dc.identifier.scopusauthoridShi, QH=8868248300en_HK
dc.identifier.scopusauthoridZeng, YX=7402981579en_HK
dc.identifier.scopusauthoridZeng, MS=10642267400en_HK

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