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Article: Anti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

TitleAnti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells
Authors
KeywordsAkt
Cancer
Resistance
Taxol
TWIST
Issue Date2007
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2007, v. 120 n. 9, p. 1891-1898 How to Cite?
AbstractTWIST, a basic helix-loop-helix transcription factor, has been reported to be associated with development and progression of human cancer. Recently, over expression of TWIST is found in cancer patients with shorter survival and poor response to chemotherapy. Previously, we found that upregulation of TWIST was responsible for the development of acquired resistance to taxol in a nasopharyngeal carcinoma (NPC) cell line, HNE1-T3 (Wang et al., Oncogene, 2004;24:274). In this study, we investigated the underlying molecular mechanisms responsible for the TWIST-mediated taxol resistance. By comparison of the parental HNE1 and its derivative HNE1-T3 cell lines, we found that the resistance to taxol in HNE1-T3 cells was associated with suppression of taxol-induced apoptosis evidenced by decreased expression of Bak and Bax and increased Bcl-2, as well as inhibition of PARP and caspase cleavage and DNA ladder formation. However, there was no correlation between taxol sensitivity and alterations on G2/M cell cycle distribution, suggesting that the TWIST-induced taxol resistance is mediated through protection against apoptosis but not mitotic arrest. Analysis of additional 8 NPC cell lines showed that upregulation of TWIST was associated with resistance to microtubule disrupting agents, especially taxol, and inactivation of TWIST through small RNA interference led to increased sensitivity to taxol-induced cell death. Subsequent studies also demonstrated that the TWIST-mediated taxol resistance may be regulated through its positive involvement with the Akt pathway. Our findings suggest an underlying molecular mechanism responsible for the TWIST-mediated chemodrug resistance and suggest a target for overcoming taxol resistance in cancer cells. © 2007 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/67410
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Xen_HK
dc.contributor.authorWang, Qen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorLeung, SCLen_HK
dc.contributor.authorWang, Xen_HK
dc.date.accessioned2010-09-06T05:54:54Z-
dc.date.available2010-09-06T05:54:54Z-
dc.date.issued2007en_HK
dc.identifier.citationInternational Journal Of Cancer, 2007, v. 120 n. 9, p. 1891-1898en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67410-
dc.description.abstractTWIST, a basic helix-loop-helix transcription factor, has been reported to be associated with development and progression of human cancer. Recently, over expression of TWIST is found in cancer patients with shorter survival and poor response to chemotherapy. Previously, we found that upregulation of TWIST was responsible for the development of acquired resistance to taxol in a nasopharyngeal carcinoma (NPC) cell line, HNE1-T3 (Wang et al., Oncogene, 2004;24:274). In this study, we investigated the underlying molecular mechanisms responsible for the TWIST-mediated taxol resistance. By comparison of the parental HNE1 and its derivative HNE1-T3 cell lines, we found that the resistance to taxol in HNE1-T3 cells was associated with suppression of taxol-induced apoptosis evidenced by decreased expression of Bak and Bax and increased Bcl-2, as well as inhibition of PARP and caspase cleavage and DNA ladder formation. However, there was no correlation between taxol sensitivity and alterations on G2/M cell cycle distribution, suggesting that the TWIST-induced taxol resistance is mediated through protection against apoptosis but not mitotic arrest. Analysis of additional 8 NPC cell lines showed that upregulation of TWIST was associated with resistance to microtubule disrupting agents, especially taxol, and inactivation of TWIST through small RNA interference led to increased sensitivity to taxol-induced cell death. Subsequent studies also demonstrated that the TWIST-mediated taxol resistance may be regulated through its positive involvement with the Akt pathway. Our findings suggest an underlying molecular mechanism responsible for the TWIST-mediated chemodrug resistance and suggest a target for overcoming taxol resistance in cancer cells. © 2007 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.subjectAkten_HK
dc.subjectCanceren_HK
dc.subjectResistanceen_HK
dc.subjectTaxolen_HK
dc.subjectTWISTen_HK
dc.subject.meshAntineoplastic Agents, Phytogenic - pharmacology-
dc.subject.meshApoptosis - drug effects-
dc.subject.meshNasopharyngeal Neoplasms - drug therapy-
dc.subject.meshNuclear Proteins - physiology-
dc.subject.meshPaclitaxel - pharmacology-
dc.titleAnti-apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=120&issue=9&spage=1891&epage=1898&date=2007&atitle=Anti-apoptotic+role+of+TWIST+and+its+association+with+Akt+pathway+in+mediating+taxol+resistance+in+nasopharyngeal+carcinoma+cellsen_HK
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_HK
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ijc.22489en_HK
dc.identifier.pmid17230521-
dc.identifier.scopuseid_2-s2.0-33947234746en_HK
dc.identifier.hkuros147313-
dc.identifier.hkuros147783-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947234746&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume120en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1891en_HK
dc.identifier.epage1898en_HK
dc.identifier.isiWOS:000244972000008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, X=8299216200en_HK
dc.identifier.scopusauthoridWang, Q=7406910452en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridLeung, SCL=36894169100en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK

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