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Article: FGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: Implication for viral-mediated FGF8b upregulation

TitleFGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: Implication for viral-mediated FGF8b upregulation
Authors
KeywordsFGF8b
LMP1
NF-κB
NPC
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2011, v. 30 n. 13, p. 1518-1530 How to Cite?
AbstractThe fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-B signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis. © 2011 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/137194
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
Funding AgencyGrant Number
Clinical Oncology, CUHK
Funding Information:

Financial support by research fund, Clinical Oncology, CUHK (VWYL). We thank Drs Q Tao and GT Chung for experimental assistance.

References

 

DC FieldValueLanguage
dc.contributor.authorLui, VWYen_HK
dc.contributor.authorYau, DMSen_HK
dc.contributor.authorCheung, CSFen_HK
dc.contributor.authorWong, SCCen_HK
dc.contributor.authorChan, AKCen_HK
dc.contributor.authorZhou, Qen_HK
dc.contributor.authorWong, EYLen_HK
dc.contributor.authorLau, CPYen_HK
dc.contributor.authorLam, EKYen_HK
dc.contributor.authorHui, EPen_HK
dc.contributor.authorHong, Ben_HK
dc.contributor.authorHui, CWCen_HK
dc.contributor.authorChan, ASKen_HK
dc.contributor.authorNg, PKSen_HK
dc.contributor.authorNg, YKen_HK
dc.contributor.authorLo, KWen_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorTsui, SKWen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorChan, ATCen_HK
dc.date.accessioned2011-08-26T14:18:35Z-
dc.date.available2011-08-26T14:18:35Z-
dc.date.issued2011en_HK
dc.identifier.citationOncogene, 2011, v. 30 n. 13, p. 1518-1530en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137194-
dc.description.abstractThe fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-B signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis. © 2011 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectFGF8ben_HK
dc.subjectLMP1en_HK
dc.subjectNF-κBen_HK
dc.subjectNPCen_HK
dc.subject.meshCell Proliferation-
dc.subject.meshFibroblast Growth Factor 8 - antagonists and inhibitors - genetics - physiology-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHerpesvirus 4, Human - pathogenicity-
dc.subject.meshOncogenes-
dc.titleFGF8b oncogene mediates proliferation and invasion of Epstein-Barr virus-associated nasopharyngeal carcinoma cells: Implication for viral-mediated FGF8b upregulationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=30&issue=13&spage=1518&epage=1530&date=2011&atitle=FGF8b+oncogene+mediates+proliferation+and+invasion+of+Epstein-Barr+virus-associated+nasopharyngeal+carcinoma+cells:+implication+for+viral-mediated+FGF8b+upregulation-
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2010.529en_HK
dc.identifier.pmid21119603-
dc.identifier.scopuseid_2-s2.0-79953189353en_HK
dc.identifier.hkuros190813en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953189353&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue13en_HK
dc.identifier.spage1518en_HK
dc.identifier.epage1530en_HK
dc.identifier.isiWOS:000288998300003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLui, VWY=7004231347en_HK
dc.identifier.scopusauthoridYau, DMS=19639624800en_HK
dc.identifier.scopusauthoridCheung, CSF=35080091300en_HK
dc.identifier.scopusauthoridWong, SCC=26039647800en_HK
dc.identifier.scopusauthoridChan, AKC=26021059700en_HK
dc.identifier.scopusauthoridZhou, Q=27068110900en_HK
dc.identifier.scopusauthoridWong, EYL=8234468400en_HK
dc.identifier.scopusauthoridLau, CPY=36608195100en_HK
dc.identifier.scopusauthoridLam, EKY=34968116400en_HK
dc.identifier.scopusauthoridHui, EP=7005081895en_HK
dc.identifier.scopusauthoridHong, B=7202125896en_HK
dc.identifier.scopusauthoridHui, CWC=40561262600en_HK
dc.identifier.scopusauthoridChan, ASK=18435746400en_HK
dc.identifier.scopusauthoridNg, PKS=54393943700en_HK
dc.identifier.scopusauthoridNg, YK=14825706500en_HK
dc.identifier.scopusauthoridLo, KW=7402101603en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridTsui, SKW=35304176500en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridChan, ATC=13404833700en_HK
dc.identifier.citeulike8379775-

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