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Article: Phospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer

TitlePhospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer
Authors
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2009, v. 28 n. 26, p. 2466-2475 How to Cite?
AbstractLocated at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis. © 2009 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/148752
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
Funding AgencyGrant Number
Chinese University of Hong Kong
National Natural Science Foundation of China30770920/C03030202
Natural Science Foundation of Zhejiang ProvinceY206090
Funding Information:

This study was supported by a grant from the Chinese University of Hong Kong, a grant from National Natural Science Foundation of China ( Grant no. 30770920/C03030202) and a grant from Natural Science Foundation of Zhejiang Province ( Grant no. Y206090).

References

 

DC FieldValueLanguage
dc.contributor.authorHu, XTen_US
dc.contributor.authorZhang, FBen_US
dc.contributor.authorFan, YCen_US
dc.contributor.authorShu, XSen_US
dc.contributor.authorWong, AHYen_US
dc.contributor.authorZhou, Wen_US
dc.contributor.authorShi, QLen_US
dc.contributor.authorTang, HMen_US
dc.contributor.authorFu, Len_US
dc.contributor.authorGuan, XYen_US
dc.contributor.authorRha, SYen_US
dc.contributor.authorTao, Qen_US
dc.contributor.authorHe, Cen_US
dc.date.accessioned2012-06-06T05:36:09Z-
dc.date.available2012-06-06T05:36:09Z-
dc.date.issued2009en_US
dc.identifier.citationOncogene, 2009, v. 28 n. 26, p. 2466-2475en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/148752-
dc.description.abstractLocated at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2′-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis. © 2009 Macmillan Publishers Limited All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshChromosomes, Human, Pair 3 - Geneticsen_US
dc.subject.meshCytoskeleton - Metabolismen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMatrix Metalloproteinase 7 - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPeritoneal Neoplasms - Genetics - Secondaryen_US
dc.subject.meshPhospholipase C Delta - Genetics - Metabolismen_US
dc.subject.meshStomach Neoplasms - Genetics - Pathologyen_US
dc.titlePhospholipase c delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric canceren_US
dc.typeArticleen_US
dc.identifier.emailFu, L:gracefu@graduate.hku.hken_US
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_US
dc.identifier.authorityFu, L=rp01435en_US
dc.identifier.authorityGuan, XY=rp00454en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2009.92en_US
dc.identifier.pmid19448674-
dc.identifier.scopuseid_2-s2.0-67650070519en_US
dc.identifier.hkuros156285-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650070519&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume28en_US
dc.identifier.issue26en_US
dc.identifier.spage2466en_US
dc.identifier.epage2475en_US
dc.identifier.isiWOS:000267601400005-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridHu, XT=14824949100en_US
dc.identifier.scopusauthoridZhang, FB=23483144100en_US
dc.identifier.scopusauthoridFan, YC=35277252300en_US
dc.identifier.scopusauthoridShu, XS=35277349300en_US
dc.identifier.scopusauthoridWong, AHY=16743208300en_US
dc.identifier.scopusauthoridZhou, W=7404516015en_US
dc.identifier.scopusauthoridShi, QL=23482928500en_US
dc.identifier.scopusauthoridTang, HM=35277565300en_US
dc.identifier.scopusauthoridFu, L=22979236700en_US
dc.identifier.scopusauthoridGuan, XY=7201463221en_US
dc.identifier.scopusauthoridRha, SY=7006023235en_US
dc.identifier.scopusauthoridTao, Q=7102578359en_US
dc.identifier.scopusauthoridHe, C=35261948900en_US

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