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Article: Downregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma.

TitleDownregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma.
Authors
Issue Date2013
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2013, v. 73 n. 7, p. 2298-2309 How to Cite?
AbstractLoss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like small GTPase DIRAS1. Downregulation of DIRAS1 occurred in approximately 50% of primary ESCCs where it was associated significantly with advanced clinical stage, lymph node metastasis, and poor overall survival. LOH and promoter methylation analyses suggested that loss of DIRAS1 expression was mediated by epigenetic mechanisms. Functional studies established that ectopic re-expression of DIRAS1 in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation. Mechanistic investigations suggested that DIRAS1 acted through extracellular signal-regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively. Taken together, our results revealed that DIRAS1 has a pivotal function in ESCC pathogenesis, with possible use as a biomarker and intervention point for new therapeutic strategies. © 2012 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/185783
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, Y-
dc.contributor.authorFu, L-
dc.contributor.authorChen, L-
dc.contributor.authorQin, YR-
dc.contributor.authorLiu, H-
dc.contributor.authorXie, FJ-
dc.contributor.authorZeng, TT-
dc.contributor.authorLI, J-
dc.contributor.authorLi, Y-
dc.contributor.authorDai, Y-
dc.contributor.authorXie, D-
dc.contributor.authorGuan, X-
dc.date.accessioned2013-08-20T11:41:12Z-
dc.date.available2013-08-20T11:41:12Z-
dc.date.issued2013-
dc.identifier.citationCancer Research, 2013, v. 73 n. 7, p. 2298-2309-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/185783-
dc.description.abstractLoss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like small GTPase DIRAS1. Downregulation of DIRAS1 occurred in approximately 50% of primary ESCCs where it was associated significantly with advanced clinical stage, lymph node metastasis, and poor overall survival. LOH and promoter methylation analyses suggested that loss of DIRAS1 expression was mediated by epigenetic mechanisms. Functional studies established that ectopic re-expression of DIRAS1 in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation. Mechanistic investigations suggested that DIRAS1 acted through extracellular signal-regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively. Taken together, our results revealed that DIRAS1 has a pivotal function in ESCC pathogenesis, with possible use as a biomarker and intervention point for new therapeutic strategies. © 2012 American Association for Cancer Research.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleDownregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma.-
dc.typeArticle-
dc.identifier.emailFu, L: gracefu@graduate.hku.hk-
dc.identifier.emailChen, L: pollyllc@hku.hk-
dc.identifier.emailGuan, X: xyguan@hkucc.hku.hk-
dc.identifier.authorityFu, L=rp01435-
dc.identifier.authorityGuan, X=rp00454-
dc.identifier.doi10.1158/0008-5472.CAN-12-2663-
dc.identifier.pmid23436800-
dc.identifier.scopuseid_2-s2.0-84875966967-
dc.identifier.hkuros218242-
dc.identifier.volume73-
dc.identifier.issue7-
dc.identifier.spage2298-
dc.identifier.epage2309-
dc.identifier.isiWOS:000316995600027-
dc.publisher.placeUnited States-

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