Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.8603
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dc.titleGelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma
dc.contributor.authorHuang, Baohua
dc.contributor.authorDENG SHUO
dc.contributor.authorLOO SER YUE
dc.contributor.authorARPITA DATTA
dc.contributor.authorYAP YAN LIN
dc.contributor.authorYan, Benedict
dc.contributor.authorOOI CHIA HUEY
dc.contributor.authorDINH THUY DUONG
dc.contributor.authorZHUO JINGLI
dc.contributor.authorLALCHHANDAMI TOCHHAWNG
dc.contributor.authorSUMA GOPINADHAN
dc.contributor.authorJegadeesan, Tamilarasi
dc.contributor.authorTAN BOON OOI,PATRICK
dc.contributor.authorSALTO-TELLEZ,MANUEL
dc.contributor.authorYONG WEI PENG
dc.contributor.authorSOONG CHUAN TECK,RICHIE
dc.contributor.authorYEOH KHAY GUAN
dc.contributor.authorGOH YAW CHONG
dc.contributor.authorPETER EDWARD LOBIE
dc.contributor.authorYANG HE
dc.contributor.authorALAN PREM KUMAR
dc.contributor.authorMaciver, Sutherland K
dc.contributor.authorSO BOK YAN,JIMMY
dc.contributor.authorYap Suen Mei,Celestial Therese
dc.date.accessioned2020-06-08T04:38:45Z
dc.date.available2020-06-08T04:38:45Z
dc.date.issued2016-05-03
dc.identifier.citationHuang, Baohua, DENG SHUO, LOO SER YUE, ARPITA DATTA, YAP YAN LIN, Yan, Benedict, OOI CHIA HUEY, DINH THUY DUONG, ZHUO JINGLI, LALCHHANDAMI TOCHHAWNG, SUMA GOPINADHAN, Jegadeesan, Tamilarasi, TAN BOON OOI,PATRICK, SALTO-TELLEZ,MANUEL, YONG WEI PENG, SOONG CHUAN TECK,RICHIE, YEOH KHAY GUAN, GOH YAW CHONG, PETER EDWARD LOBIE, YANG HE, ALAN PREM KUMAR, Maciver, Sutherland K, SO BOK YAN,JIMMY, Yap Suen Mei,Celestial Therese (2016-05-03). Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma. ONCOTARGET 7 (18) : 25391-25407. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.8603
dc.identifier.issn1949-2553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/169499
dc.description.abstractIn 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.language.isoen
dc.publisherIMPACT JOURNALS LLC
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectOncology
dc.subjectCell Biology
dc.subjectgelsolin
dc.subjectgastric cancer
dc.subjectE-Cadherin
dc.subjecthepatocyte growth factor (HGF)
dc.subjectcancer invasion
dc.subjectEPITHELIAL-MESENCHYMAL TRANSITION
dc.subjectC-MET EXPRESSION
dc.subjectE-CADHERIN
dc.subjectPROGNOSTIC-SIGNIFICANCE
dc.subjectCANCER-CELL
dc.subjectDOWN-REGULATION
dc.subjectUP-REGULATION
dc.subjectDIFFUSE
dc.subjectAMPLIFICATION
dc.subjectINVASION
dc.typeArticle
dc.date.updated2020-06-07T11:12:08Z
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentMEDICINE
dc.contributor.departmentPHYSIOLOGY
dc.contributor.departmentSURGERY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.18632/oncotarget.8603
dc.description.sourcetitleONCOTARGET
dc.description.volume7
dc.description.issue18
dc.description.page25391-25407
dc.description.placeUnited States
dc.published.statePublished
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