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Article: Four and a half LIM protein 2 (FHL2) negatively regulates the transcription of E-cadherin through interaction with Snail1

TitleFour and a half LIM protein 2 (FHL2) negatively regulates the transcription of E-cadherin through interaction with Snail1
Authors
KeywordsColon cancer
E-cadherin
Epithelial-mesenchymal transition
FHL2
Snail1
Issue Date2011
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
Citation
European Journal Of Cancer, 2011, v. 47 n. 1, p. 121-130 How to Cite?
AbstractE-cadherin is a hallmark of epithelial-mesenchymal transition (EMT), which plays a crucial role in cancer metastasis. We previously demonstrated that four and a half LIM protein 2 (FHL2) inhibited E-cadherin expression and promoted invasive potential and EMT in colon cancer. Here, we aim to further define the mechanism underlying the inhibition of E-cadherin by FHL2 in colon cancer. The expression profiles of FHL2 and Snail1 were first observed by Western blot, immunofluorescence and immunohistochemistry. We found that both the protein level and the cellular localisation of Snail1 were quite similar to FHL2 in colon cancer; reciprocal co-immunoprecipitation assay showed that FHL2 was able to bind Snail1 and its intact structure was required. The expression of FHL2 was positively correlated to Snail1 while negatively to E-cadherin and phospho-Snail1. FHL2 over-expression induced the accumulation of Snail1 in the nucleus. Moreover, dual luciferase assay revealed that FHL2 over-expression decreased while FHL2 siRNA increased the transcriptional activities of two E-cadherin promoter constructs which contained E-box sites (Snail1-binding elements). Mutation of E-boxes increased the transcriptional activities and FHL2 expression was involved in the function of mutation. These results suggested that FHL2 negatively regulated E-cadherin transcriptional activity through interaction with Snail1. Our study established a novel regulatory function of FHL2 and revealed a potential mechanism on promoting the process of EMT. © 2010 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/133639
ISSN
2015 Impact Factor: 6.163
2015 SCImago Journal Rankings: 3.152
ISI Accession Number ID
Funding AgencyGrant Number
Simon K.Y. Lee Gastroenterology Research Fund
Gordon Chiu stomach cancer research fund
University of Hong Kong
Research Grant Council of Hong Kong Special Administrative RegionHKU7785/09M
French Agence National de la recherche (ANR)
Fondation pour la Recherche M'dicale (FRM)
National Natural Science Foundation of China30973404
Funding Information:

Supported by the Simon K.Y. Lee Gastroenterology Research Fund, the Gordon Chiu stomach cancer research fund, University of Hong Kong, the grants from the Research Grant Council of Hong Kong Special Administrative Region to Dr. J. Wang (HKU7785/09M) and the grants to C. Sardet from the French Agence National de la recherche (ANR), the Fondation pour la Recherche M'dicale (FRM) and from the National Natural Science Foundation of China (30973404).

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Wen_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorSardet, Cen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorLam, CSCen_HK
dc.contributor.authorNg, Len_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorHung, IFNen_HK
dc.contributor.authorTan, VPYen_HK
dc.contributor.authorJiang, Ben_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2011-05-24T02:12:47Z-
dc.date.available2011-05-24T02:12:47Z-
dc.date.issued2011en_HK
dc.identifier.citationEuropean Journal Of Cancer, 2011, v. 47 n. 1, p. 121-130en_HK
dc.identifier.issn0959-8049en_HK
dc.identifier.urihttp://hdl.handle.net/10722/133639-
dc.description.abstractE-cadherin is a hallmark of epithelial-mesenchymal transition (EMT), which plays a crucial role in cancer metastasis. We previously demonstrated that four and a half LIM protein 2 (FHL2) inhibited E-cadherin expression and promoted invasive potential and EMT in colon cancer. Here, we aim to further define the mechanism underlying the inhibition of E-cadherin by FHL2 in colon cancer. The expression profiles of FHL2 and Snail1 were first observed by Western blot, immunofluorescence and immunohistochemistry. We found that both the protein level and the cellular localisation of Snail1 were quite similar to FHL2 in colon cancer; reciprocal co-immunoprecipitation assay showed that FHL2 was able to bind Snail1 and its intact structure was required. The expression of FHL2 was positively correlated to Snail1 while negatively to E-cadherin and phospho-Snail1. FHL2 over-expression induced the accumulation of Snail1 in the nucleus. Moreover, dual luciferase assay revealed that FHL2 over-expression decreased while FHL2 siRNA increased the transcriptional activities of two E-cadherin promoter constructs which contained E-box sites (Snail1-binding elements). Mutation of E-boxes increased the transcriptional activities and FHL2 expression was involved in the function of mutation. These results suggested that FHL2 negatively regulated E-cadherin transcriptional activity through interaction with Snail1. Our study established a novel regulatory function of FHL2 and revealed a potential mechanism on promoting the process of EMT. © 2010 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejcaen_HK
dc.relation.ispartofEuropean Journal of Canceren_HK
dc.subjectColon canceren_HK
dc.subjectE-cadherinen_HK
dc.subjectEpithelial-mesenchymal transitionen_HK
dc.subjectFHL2en_HK
dc.subjectSnail1en_HK
dc.subject.meshCadherins - antagonists and inhibitors - genetics-
dc.subject.meshColonic Neoplasms - etiology - metabolism-
dc.subject.meshHomeodomain Proteins - physiology-
dc.subject.meshMuscle Proteins - physiology-
dc.subject.meshTranscription Factors - metabolism - physiology-
dc.titleFour and a half LIM protein 2 (FHL2) negatively regulates the transcription of E-cadherin through interaction with Snail1en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0959-8049&volume=47&issue=1&spage=121&epage=130&date=2011&atitle=Four+and+a+half+LIM+protein+2+(FHL2)+negatively+regulates+the+transcription+of+E-cadherin+through+interaction+with+Snail1-
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailPang, R: robertap@hku.hken_HK
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hken_HK
dc.identifier.emailTan, VPY: vpytan@hku.hken_HK
dc.identifier.emailWong, BCY: bcywong@hku.hken_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityHung, IFN=rp00508en_HK
dc.identifier.authorityTan, VPY=rp01458en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ejca.2010.07.045en_HK
dc.identifier.pmid20801642-
dc.identifier.scopuseid_2-s2.0-78650417038en_HK
dc.identifier.hkuros185100en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650417038&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume47en_HK
dc.identifier.issue1en_HK
dc.identifier.spage121en_HK
dc.identifier.epage130en_HK
dc.identifier.isiWOS:000286774700014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZhang, W=7409428339en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridSardet, C=7005616535en_HK
dc.identifier.scopusauthoridLi, J=7410060376en_HK
dc.identifier.scopusauthoridLam, CSC=35332626500en_HK
dc.identifier.scopusauthoridNg, L=36450962500en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridHung, IFN=7006103457en_HK
dc.identifier.scopusauthoridTan, VPY=24449627600en_HK
dc.identifier.scopusauthoridJiang, B=34770534200en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.citeulike7833379-

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