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Article: K252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma cells

TitleK252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma cells
Authors
KeywordsAnoikis-sensitization
BDNF
K252a
Nasopharyngeal carcinoma (NPC)
TrkB tyrosine kinase
Issue Date2012
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6997
Citation
Investigational New Drugs, 2012, v. 30 n. 1, p. 48-58 How to Cite?
AbstractRecent studies revealed an unexpected role of the neurotrophin receptor pathway, BDNF/TrkB signaling, in cancer metastasis and anoikis (i.e. detachment-induced cell death). Survival of cancer cells in detached state (known as anoikis-resistance) is known to be pre-requisite for metastasis. Nasopharyngeal carcinoma (NPC), an endemic head and neck cancer in Southeast Asia, is highly invasive, metastatic, and etiologically associated with Epstein-Barr virus (EBV, an oncovirus) infection. Mechanistic studies on the invasive/metastatic nature of NPC can facilitate the development of anti-metastatic therapy in NPC. Thus far, the role of BDNF/TrkB signaling in virus-associated human cancer is unclear. Here, using multiple cell line models of NPC with EBV-association (HONE-1-EBV, HK1-LMP1 and C666-1), we investigated the potential involvement of BDNF/TrkB signaling in cellular migration and anoikis-resistant characteristics of NPC. We found that all three EBV-associated NPC cell lines tested were intrinsically anoikis-resistant (i.e. survived in detached state) and expressed both BDNF and TrkB. BDNF stimulation induced cellular migration, but not proliferation of these cells. Further, we examined if pharmacologic targeting of anoikis-resistance of NPC cells can be achievable by a proof-of-concept Trk inhibitor, K252a, in these EBV-associated NPC models. Our results demonstrated that K252a, was able to attenuate BDNFinduced migration and proliferation of NPC cells. More importantly, we demonstrated for the first time that K252a harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against EBVassociated human cancer cells, namely NPC cells. This proofof- concept study demonstrated that K252a, a Trk inhibitor, can potentially be used as an anoikis-sensitizing agent in NPC. © Springer Science+Business Media, LLC 2010.
Persistent Identifierhttp://hdl.handle.net/10722/137203
ISSN
2015 Impact Factor: 3.281
2015 SCImago Journal Rankings: 1.376
ISI Accession Number ID
Funding AgencyGrant Number
Chinese University of Hong Kong2008.1.101
Funding Information:

This study was supported by Direct Grant for Research, The Chinese University of Hong Kong (2008.1.101 to YKN). Result of this study was presented in part in the poster session at the American Association of Cancer Research (AACR) annual meeting, Colorado, USA, 2009.

References

 

DC FieldValueLanguage
dc.contributor.authorNg, YKen_HK
dc.contributor.authorWong, EYLen_HK
dc.contributor.authorLau, CPYen_HK
dc.contributor.authorChan, JPLen_HK
dc.contributor.authorWong, SCCen_HK
dc.contributor.authorChan, ASKen_HK
dc.contributor.authorKwan, MPCen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorLai, PBSen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorLui, VWYen_HK
dc.date.accessioned2011-08-26T14:18:46Z-
dc.date.available2011-08-26T14:18:46Z-
dc.date.issued2012en_HK
dc.identifier.citationInvestigational New Drugs, 2012, v. 30 n. 1, p. 48-58en_HK
dc.identifier.issn0167-6997en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137203-
dc.description.abstractRecent studies revealed an unexpected role of the neurotrophin receptor pathway, BDNF/TrkB signaling, in cancer metastasis and anoikis (i.e. detachment-induced cell death). Survival of cancer cells in detached state (known as anoikis-resistance) is known to be pre-requisite for metastasis. Nasopharyngeal carcinoma (NPC), an endemic head and neck cancer in Southeast Asia, is highly invasive, metastatic, and etiologically associated with Epstein-Barr virus (EBV, an oncovirus) infection. Mechanistic studies on the invasive/metastatic nature of NPC can facilitate the development of anti-metastatic therapy in NPC. Thus far, the role of BDNF/TrkB signaling in virus-associated human cancer is unclear. Here, using multiple cell line models of NPC with EBV-association (HONE-1-EBV, HK1-LMP1 and C666-1), we investigated the potential involvement of BDNF/TrkB signaling in cellular migration and anoikis-resistant characteristics of NPC. We found that all three EBV-associated NPC cell lines tested were intrinsically anoikis-resistant (i.e. survived in detached state) and expressed both BDNF and TrkB. BDNF stimulation induced cellular migration, but not proliferation of these cells. Further, we examined if pharmacologic targeting of anoikis-resistance of NPC cells can be achievable by a proof-of-concept Trk inhibitor, K252a, in these EBV-associated NPC models. Our results demonstrated that K252a, was able to attenuate BDNFinduced migration and proliferation of NPC cells. More importantly, we demonstrated for the first time that K252a harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against EBVassociated human cancer cells, namely NPC cells. This proofof- concept study demonstrated that K252a, a Trk inhibitor, can potentially be used as an anoikis-sensitizing agent in NPC. © Springer Science+Business Media, LLC 2010.en_HK
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-6997en_HK
dc.relation.ispartofInvestigational New Drugsen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.subjectAnoikis-sensitizationen_HK
dc.subjectBDNFen_HK
dc.subjectK252aen_HK
dc.subjectNasopharyngeal carcinoma (NPC)en_HK
dc.subjectTrkB tyrosine kinaseen_HK
dc.titleK252a induces anoikis-sensitization with suppression of cellular migration in Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10637-010-9513-4en_HK
dc.identifier.pmid20694504-
dc.identifier.scopuseid_2-s2.0-84856529862en_HK
dc.identifier.hkuros191875en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84856529862&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue1en_HK
dc.identifier.spage48en_HK
dc.identifier.epage58en_HK
dc.identifier.isiWOS:000299121500006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNg, YK=14825706500en_HK
dc.identifier.scopusauthoridWong, EYL=8234468400en_HK
dc.identifier.scopusauthoridLau, CPY=36608195100en_HK
dc.identifier.scopusauthoridChan, JPL=35298394000en_HK
dc.identifier.scopusauthoridWong, SCC=26039647800en_HK
dc.identifier.scopusauthoridChan, ASK=18435746400en_HK
dc.identifier.scopusauthoridKwan, MPC=36198474100en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridLai, PBS=7202946421en_HK
dc.identifier.scopusauthoridChan, ATC=13404833700en_HK
dc.identifier.scopusauthoridLui, VWY=7004231347en_HK
dc.identifier.citeulike7663732-

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