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Article: Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth

TitleActivation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth
Authors
Keywords5-LOX
E-cadherin
EMT
Gastric cancer
Nicotine
Snail
Issue Date2010
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2010, v. 292 n. 2, p. 237-245 How to Cite?
AbstractNicotine is shown to be one of the carcinogenic agents for gastric cancer. Perturbation of epithelial-mesenchymal transition (EMT) results in loss of intracellular adhesions leading to tumor progression. In this study, we examined the underlying mechanism of the long-term effects of nicotine on tumor progression in human gastric cancer cells. Nicotine activated 5-lipoxygenase (5-LOX) in three gastric cancer cell lines (MKN-45, MKN-28 and AGS). Cells treated with nicotine dose- and time-dependently induced cell proliferation, invasion and suppressed apoptosis. In addition, cell cycle progression analysis revealed that activation of 5-LOX modulated the G1/S phase transition regulatory proteins and caused cell proliferation. MK886 (5-LOX activating protein inhibitor) mediated the induction of apoptosis by elevation of caspase-3 and Bax/Bcl2 ratio. Abrogation of 5-LOX repressed featured molecular markers of EMT (inactivation of E-cadherin and activation of transcriptional repressor Snail). Blockade of 5-LOX signaling resulted in downregulation of cyclin D1, matrix metalloproteinase (MMP-7, -9), urokinase plasminogen activator (uPA) and its receptor (uPAR), and pro-apoptotic proteins. Furthermore, suppression of Snail and induction of E-cadherin is extracellular signal-regulated kinase (Erk)-dependent. Thus, we conclude that the promotion effect of nicotine on cancer cell progression and EMT is mediated by Erk/5-LOX signaling pathway. © 2009 Elsevier Ireland Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/125436
ISSN
2015 Impact Factor: 5.992
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID
Funding AgencyGrant Number
Chinese University of Hong Kong
Funding Information:

The project was supported by the Research Funding from the Chinese University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorShin, VYen_HK
dc.contributor.authorJin, HCen_HK
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorCho, CHen_HK
dc.date.accessioned2010-10-31T11:31:19Z-
dc.date.available2010-10-31T11:31:19Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Letters, 2010, v. 292 n. 2, p. 237-245en_HK
dc.identifier.issn0304-3835en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125436-
dc.description.abstractNicotine is shown to be one of the carcinogenic agents for gastric cancer. Perturbation of epithelial-mesenchymal transition (EMT) results in loss of intracellular adhesions leading to tumor progression. In this study, we examined the underlying mechanism of the long-term effects of nicotine on tumor progression in human gastric cancer cells. Nicotine activated 5-lipoxygenase (5-LOX) in three gastric cancer cell lines (MKN-45, MKN-28 and AGS). Cells treated with nicotine dose- and time-dependently induced cell proliferation, invasion and suppressed apoptosis. In addition, cell cycle progression analysis revealed that activation of 5-LOX modulated the G1/S phase transition regulatory proteins and caused cell proliferation. MK886 (5-LOX activating protein inhibitor) mediated the induction of apoptosis by elevation of caspase-3 and Bax/Bcl2 ratio. Abrogation of 5-LOX repressed featured molecular markers of EMT (inactivation of E-cadherin and activation of transcriptional repressor Snail). Blockade of 5-LOX signaling resulted in downregulation of cyclin D1, matrix metalloproteinase (MMP-7, -9), urokinase plasminogen activator (uPA) and its receptor (uPAR), and pro-apoptotic proteins. Furthermore, suppression of Snail and induction of E-cadherin is extracellular signal-regulated kinase (Erk)-dependent. Thus, we conclude that the promotion effect of nicotine on cancer cell progression and EMT is mediated by Erk/5-LOX signaling pathway. © 2009 Elsevier Ireland Ltd.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canleten_HK
dc.relation.ispartofCancer Lettersen_HK
dc.subject5-LOXen_HK
dc.subjectE-cadherinen_HK
dc.subjectEMTen_HK
dc.subjectGastric canceren_HK
dc.subjectNicotineen_HK
dc.subjectSnailen_HK
dc.subject.meshArachidonate 5-Lipoxygenase - metabolism-
dc.subject.meshEpithelial Cells - cytology-
dc.subject.meshMesoderm - cytology-
dc.subject.meshNicotine - pharmacology-
dc.subject.meshStomach Neoplasms - enzymology - pathology-
dc.titleActivation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growthen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1872-7980 (Electronic)1872-7980 (Linkin&volume=&spage=&epage=&date=2010&atitle=Activation+of+5-lipoxygenase+is+required+for+nicotine+mediated+epithelial-mesenchymal+transition+and+tumor+cell+growthen_HK
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.canlet.2009.12.011en_HK
dc.identifier.pmid20061081en_HK
dc.identifier.scopuseid_2-s2.0-77951883817en_HK
dc.identifier.hkuros181359en_HK
dc.identifier.hkuros172812-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951883817&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume292en_HK
dc.identifier.issue2en_HK
dc.identifier.spage237en_HK
dc.identifier.epage245en_HK
dc.identifier.eissn1872-7980-
dc.identifier.isiWOS:000277900800012-
dc.publisher.placeIrelanden_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridJin, HC=24577511700en_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridCho, CH=14067000400en_HK
dc.identifier.citeulike6550615-

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