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Article: Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma

TitleIdentification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma
Authors
KeywordsCell Cycle
Epigenetic Regulation
Gene Expression
Signal Transduction
Issue Date2012
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2012, v. 143 n. 3, p. 675-686.e12 How to Cite?
AbstractBACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most commonly observed histologic subtype of esophageal cancer. ESCC is believed to develop via accumulation of numerous genetic alterations, including inactivation of tumor suppressor genes and activation of oncogenes. We searched for transcripts that were altered in human ESCC samples compared with nontumor tissues. METHODS: We performed integrative transcriptome sequencing (RNA-Seq) analysis using ESCC samples from 3 patients and adjacent nontumor tissues to identify transcripts that were altered in ESCC tissue. We performed molecular and functional studies of the transcripts identified and investigated the mechanisms of alteration. RESULTS: We identified protein tyrosine kinase 6 (PTK6) as a transcript that was significantly down-regulated in ESCC tissues and cell lines compared with nontumor tissues or immortalized normal esophageal cell lines. The promoter of the PTK6 gene was inactivated in ESCC tissues at least in part via hypermethylation and histone deacetylation. Knockdown of PTK6 in KYSE30 ESCC cells using small hairpin RNAs increased their ability to form foci, migrate, and invade extracellular matrix in culture and form tumors in nude mice. Overexpression of PTK6 in these cells reduced their proliferation in culture and tumor formation in mice. PTK6 reduced phosphorylation of Akt and glycogen synthase kinase (GSK)3β, leading to activation of β-catenin. CONCLUSIONS: PTK6 was identified as a transcript that is down-regulated in human ESCC tissues via epigenetic modification at the PTK6 locus. Its product appears to regulate cell proliferation by reducing phosphorylation of Akt and GSK3β, leading to activation of β-catenin. Reduced levels of PTK6 promote growth of xenograft tumors in mice; it might be developed as a marker of ESCC. © 2012 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/152624
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMa, Sen_HK
dc.contributor.authorBao, JYJen_HK
dc.contributor.authorKwan, PSen_HK
dc.contributor.authorChan, YPen_HK
dc.contributor.authorTong, CMen_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorZhang, Nen_HK
dc.contributor.authorTong, AHYen_HK
dc.contributor.authorQin, YRen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorLok, Sen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2012-07-16T09:44:15Z-
dc.date.available2012-07-16T09:44:15Z-
dc.date.issued2012en_HK
dc.identifier.citationGastroenterology, 2012, v. 143 n. 3, p. 675-686.e12en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152624-
dc.description.abstractBACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the most commonly observed histologic subtype of esophageal cancer. ESCC is believed to develop via accumulation of numerous genetic alterations, including inactivation of tumor suppressor genes and activation of oncogenes. We searched for transcripts that were altered in human ESCC samples compared with nontumor tissues. METHODS: We performed integrative transcriptome sequencing (RNA-Seq) analysis using ESCC samples from 3 patients and adjacent nontumor tissues to identify transcripts that were altered in ESCC tissue. We performed molecular and functional studies of the transcripts identified and investigated the mechanisms of alteration. RESULTS: We identified protein tyrosine kinase 6 (PTK6) as a transcript that was significantly down-regulated in ESCC tissues and cell lines compared with nontumor tissues or immortalized normal esophageal cell lines. The promoter of the PTK6 gene was inactivated in ESCC tissues at least in part via hypermethylation and histone deacetylation. Knockdown of PTK6 in KYSE30 ESCC cells using small hairpin RNAs increased their ability to form foci, migrate, and invade extracellular matrix in culture and form tumors in nude mice. Overexpression of PTK6 in these cells reduced their proliferation in culture and tumor formation in mice. PTK6 reduced phosphorylation of Akt and glycogen synthase kinase (GSK)3β, leading to activation of β-catenin. CONCLUSIONS: PTK6 was identified as a transcript that is down-regulated in human ESCC tissues via epigenetic modification at the PTK6 locus. Its product appears to regulate cell proliferation by reducing phosphorylation of Akt and GSK3β, leading to activation of β-catenin. Reduced levels of PTK6 promote growth of xenograft tumors in mice; it might be developed as a marker of ESCC. © 2012 AGA Institute.en_HK
dc.languageengen_US
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subjectCell Cycleen_HK
dc.subjectEpigenetic Regulationen_HK
dc.subjectGene Expressionen_HK
dc.subjectSignal Transductionen_HK
dc.titleIdentification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailMa, S: stefma@hku.hken_HK
dc.identifier.emailFu, L: gracelfu@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailLok, S: silok@genome.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityMa, S=rp00506en_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityLok, S=rp00271en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1053/j.gastro.2012.06.007en_HK
dc.identifier.pmid22705009-
dc.identifier.scopuseid_2-s2.0-84865468504en_HK
dc.identifier.hkuros201805en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84865468504&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume143en_HK
dc.identifier.issue3en_HK
dc.identifier.spage675en_HK
dc.identifier.epage686.e12en_HK
dc.identifier.eissn1528-0012-
dc.identifier.isiWOS:000312158700016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMa, S=16444895800en_HK
dc.identifier.scopusauthoridBao, JYJ=45960893700en_HK
dc.identifier.scopusauthoridKwan, PS=36698058700en_HK
dc.identifier.scopusauthoridChan, YP=14009821700en_HK
dc.identifier.scopusauthoridTong, CM=46062579200en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridZhang, N=55261475000en_HK
dc.identifier.scopusauthoridTong, AHY=55314966000en_HK
dc.identifier.scopusauthoridQin, YR=7403100680en_HK
dc.identifier.scopusauthoridTsao, SW=55311525100en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridLok, S=21035019900en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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