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Article: WNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma

TitleWNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinoma
Authors
KeywordsEsophageal squamous cell carcinoma
Methylation
Tumor suppressor gene
WNT signaling
WNT5A
Issue Date2010
PublisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/cbt/index.php
Citation
Cancer Biology And Therapy, 2010, v. 10 n. 6, p. 617-624 How to Cite?
AbstractWNT5A is classified as a non-transforming WNT family member whose role in carcinogenesis is still ambiguous. It exhibits tumor suppressor activities in some cancers (thyroid, brain, breast and colorectum), but is aberrantly upregulated in cancers of lung, stomach and prostate. We investigated its epigenetic alterations and functions in esophageal squamous cell carcinoma (ESCC). With semi-quantitative reverse transcription PCR, we found that WNT5A was silenced or downregulated in 5 of 18 ESCC cell lines, but expressed in normal esophagus tissue and immortalized normal esophageal epithelial cell lines. promoter cpG methylation of WNT5A was detected in 4 of the 5 downregulated ESCC cell lines, while 5-aza-2′-deoxycytidine treatment induced WNT5A expression and demethylated its promoter in silenced cell lines. WNT5A promoter methylation was frequently detected in primary ESCC (24/36, 67%), but less frequently and weakly in paired surgical marginal esophageal tissues (8/36, 22%; p < 0.01), while no methylation was detected in seven normal esophageal epithelial tissues from healthy donors. ectopic expression of WNT5A resulted in significant inhibition of clonogenicity and motility of ESCC cells, accompanied by a dramatic decrease of intracellular β-catenin protein level and β-catenin transcriptional activity. In summary, we show that WNT5A is frequently silenced in ESCC by promoter methylation and exhibits tumor suppressor properties through antagonizing the WNT/β-catenin pathway. The epigenetic disruption of WNT5A would thus contribute directly to the aberrant activation of WNT/β-catenin signaling during ESCC pathogenesis. © 2010 Landes Bioscience.
Persistent Identifierhttp://hdl.handle.net/10722/129517
ISSN
2015 Impact Factor: 2.921
2015 SCImago Journal Rankings: 1.297
ISI Accession Number ID
Funding AgencyGrant Number
CUHK
Hong Kong RGCCA06/07.SC03
National Natural Science Foundation of China30801344
Funding Information:

This project was supported by the CUHK Focused Research Investment Scheme C, a Hong Kong RGC Central Allocation Grant (CA06/07.SC03, Q. T.) and National Natural Science Foundation of China (30801344). We thank Drs. George Tsao and Vivian Lui for some normal cell lines, DSMZ (German Collection of Microorganisms & Cell Cultures) for the KYSE cell lines (Shimada et al. Cancer 1992; 69: 277-84) and Prof. Christof Niehrs (German Cancer Research Center DKFZ, Heidelberg, Germany) for the pTOPFLASH plasmid.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Jen_HK
dc.contributor.authorYing, Jen_HK
dc.contributor.authorFan, Yen_HK
dc.contributor.authorWu, Len_HK
dc.contributor.authorYing, Yen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-12-23T08:38:21Z-
dc.date.available2010-12-23T08:38:21Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Biology And Therapy, 2010, v. 10 n. 6, p. 617-624en_HK
dc.identifier.issn1538-4047en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129517-
dc.description.abstractWNT5A is classified as a non-transforming WNT family member whose role in carcinogenesis is still ambiguous. It exhibits tumor suppressor activities in some cancers (thyroid, brain, breast and colorectum), but is aberrantly upregulated in cancers of lung, stomach and prostate. We investigated its epigenetic alterations and functions in esophageal squamous cell carcinoma (ESCC). With semi-quantitative reverse transcription PCR, we found that WNT5A was silenced or downregulated in 5 of 18 ESCC cell lines, but expressed in normal esophagus tissue and immortalized normal esophageal epithelial cell lines. promoter cpG methylation of WNT5A was detected in 4 of the 5 downregulated ESCC cell lines, while 5-aza-2′-deoxycytidine treatment induced WNT5A expression and demethylated its promoter in silenced cell lines. WNT5A promoter methylation was frequently detected in primary ESCC (24/36, 67%), but less frequently and weakly in paired surgical marginal esophageal tissues (8/36, 22%; p < 0.01), while no methylation was detected in seven normal esophageal epithelial tissues from healthy donors. ectopic expression of WNT5A resulted in significant inhibition of clonogenicity and motility of ESCC cells, accompanied by a dramatic decrease of intracellular β-catenin protein level and β-catenin transcriptional activity. In summary, we show that WNT5A is frequently silenced in ESCC by promoter methylation and exhibits tumor suppressor properties through antagonizing the WNT/β-catenin pathway. The epigenetic disruption of WNT5A would thus contribute directly to the aberrant activation of WNT/β-catenin signaling during ESCC pathogenesis. © 2010 Landes Bioscience.en_HK
dc.languageengen_US
dc.publisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/cbt/index.phpen_HK
dc.relation.ispartofCancer Biology and Therapyen_HK
dc.subjectEsophageal squamous cell carcinomaen_HK
dc.subjectMethylationen_HK
dc.subjectTumor suppressor geneen_HK
dc.subjectWNT signalingen_HK
dc.subjectWNT5Aen_HK
dc.subject.meshDNA Methylation-
dc.subject.meshProto-Oncogene Proteins - genetics - metabolism-
dc.subject.meshSignal Transduction - genetics-
dc.subject.meshWnt Proteins - genetics - metabolism-
dc.subject.meshbeta Catenin - genetics - metabolism-
dc.titleWNT5A antagonizes WNT/β-catenin signaling and is frequently silenced by promoter CpG methylation in esophageal squamous cell carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1538-4047&volume=10&issue=6&spage=617&epage=624&date=2010&atitle=WNT5A+antagonizes+WNT/β-catenin+signaling+and+is+frequently+silenced+by+promoter+CpG+methylation+in+esophageal+squamous+cell+carcinoma-
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4161/cbt.10.6.12609en_HK
dc.identifier.pmid20603606-
dc.identifier.scopuseid_2-s2.0-77957141708en_HK
dc.identifier.hkuros176924en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957141708&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue6en_HK
dc.identifier.spage617en_HK
dc.identifier.epage624en_HK
dc.identifier.isiWOS:000281909500014-
dc.publisher.placeUnited Statesen_HK

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