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dc.contributor.authorLi, Bin
dc.contributor.authorXu, Wen Wen
dc.contributor.authorLam, Alfred King Y
dc.contributor.authorWang, Yang
dc.contributor.authorHu, Hui-Fang
dc.contributor.authorGuan, Xin Yuan
dc.contributor.authorQin, Yan Ru
dc.contributor.authorSaremi, Nassim
dc.contributor.authorTsao, Sai Wah
dc.contributor.authorHe, Qing-Yu
dc.contributor.authorCheung, Annie LM
dc.date.accessioned2017-12-11T00:49:54Z
dc.date.available2017-12-11T00:49:54Z
dc.date.issued2017
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.16333
dc.identifier.urihttp://hdl.handle.net/10072/355158
dc.description.abstractMetastasis is the most lethal hallmark of esophageal squamous cell carcinoma (ESCC). The aim of the study is to identify key signaling pathways that control metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were established through three rounds of selection of cancer cells invading through matrigel-coated chambers. Gene expression profile of one of the I3 sublines was compared with that of its parental cell line using cDNA microarray analysis. Gene ontology and pathway analyses of the differentially expressed genes (both upregulated and downregulated) indicated that genes associated with cellular movement and the AKT pathway were associated with increased cancer cell invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p-AKT), N-cadherin and decreased E-cadherin expression in the I3 cells. Immunohistochemistry was used to evaluate the clinical significance of p-AKT expression in ESCC, and the results showed higher p-AKT nuclear expression in lymph node metastases when compared with primary carcinoma. Inactivation of the PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted in reversed cadherin switching and inhibited cancer cell motility. Inhibition of the pathway by treatment with wortmannin markedly suppressed experimental metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic target in treatment of metastatic ESCC.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherImpact Journals LLC
dc.relation.ispartofpagefrom38755
dc.relation.ispartofpageto38766
dc.relation.ispartofissue24
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume8
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchOncology and carcinogenesis not elsewhere classified
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321199
dc.titleSignificance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by/3.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Li et al 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY),which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorLam, Alfred K.


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