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dc.contributor.authorHuang, B.
dc.contributor.authorDeng, S.
dc.contributor.authorLoo, S.
dc.contributor.authorDatta, A.
dc.contributor.authorYap, Y.
dc.contributor.authorYan, B.
dc.contributor.authorOoi, C.
dc.contributor.authorDinh, T.
dc.contributor.authorZhuo, J.
dc.contributor.authorTochhawng, L.
dc.contributor.authorGopinadhan, S.
dc.contributor.authorJegadeesan, T.
dc.contributor.authorTan, P.
dc.contributor.authorSalto-Tellez, M.
dc.contributor.authorYong, W.
dc.contributor.authorSoong, R.
dc.contributor.authorYeoh, K.
dc.contributor.authorGoh, Y.
dc.contributor.authorLobie, P.
dc.contributor.authorYang, H.
dc.contributor.authorKumar, Alan Prem
dc.contributor.authorMaciver, S.
dc.contributor.authorSo, J.
dc.contributor.authorYap, C.
dc.date.accessioned2017-04-04T02:46:22Z
dc.date.available2017-04-04T02:46:22Z
dc.date.created2017-04-03T10:56:21Z
dc.date.issued2016
dc.identifier.citationHuang, B. and Deng, S. and Loo, S. and Datta, A. and Yap, Y. and Yan, B. and Ooi, C. et al. 2016. Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma. Oncotarget. 7 (18): pp. 25391-25407.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/51736
dc.identifier.doi10.18632/oncotarget.8603
dc.description.abstract

In gastric cancer (GC), the main subtypes (diffuse and intestinal types) differ in pathological characteristics, with diffuse GC exhibiting early disseminative and invasive behaviour. A distinctive feature of diffuse GC is loss of intercellular adhesion. Although widely attributed to mutations in the CDH1 gene encoding E-cadherin, a significant percentage of diffuse GC do not harbor CDH1 mutations. We found that the expression of the actin-modulating cytoskeletal protein, gelsolin, is significantly higher in diffuse-type compared to intestinal-type GCs, using immunohistochemical and microarray analysis. Furthermore, in GCs with wild-type CDH1, gelsolin expression correlated inversely with CDH1 gene expression. Downregulating gelsolin using siRNA in GC cells enhanced intercellular adhesion and E-cadherin expression, and reduced invasive capacity. Interestingly, hepatocyte growth factor (HGF) induced increasedgelsolin expression, and gelsolin was essential for HGF-medicated cell scattering and E-cadherin transcriptional repression through Snail, Twist and Zeb2. The HGF-dependent effect on E-cadherin was found to be mediated by interactions between gelsolin and PI3K-Akt signaling. This study reveals for the first time a function of gelsolin in the HGF/cMet oncogenic pathway, which leads to E-cadherin repression and cell scattering in gastric cancer. Our study highlights gelsolin as an important pro-disseminative factor contributing to the aggressive phenotype of diffuse GC.

dc.publisherImpact Journals LLC
dc.titleGelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma
dc.typeJournal Article
dcterms.source.volume7
dcterms.source.number18
dcterms.source.startPage25391
dcterms.source.endPage25407
dcterms.source.issn1949-2553
dcterms.source.titleOncotarget
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access via publisher


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