Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.8603
Title: | Gelsolin-mediated activation of PI3K/Akt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric carcinoma | Authors: | Huang, 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 |
Keywords: | Science & Technology Life Sciences & Biomedicine Oncology Cell Biology gelsolin gastric cancer E-Cadherin hepatocyte growth factor (HGF) cancer invasion EPITHELIAL-MESENCHYMAL TRANSITION C-MET EXPRESSION E-CADHERIN PROGNOSTIC-SIGNIFICANCE CANCER-CELL DOWN-REGULATION UP-REGULATION DIFFUSE AMPLIFICATION INVASION |
Issue Date: | 3-May-2016 | Publisher: | IMPACT JOURNALS LLC | Citation: | Huang, 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 | 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. | Source Title: | ONCOTARGET | URI: | https://scholarbank.nus.edu.sg/handle/10635/169499 | ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.8603 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
Gelsolin-mediated activation of PI3KAkt pathway is crucial for hepatocyte growth factor-induced cell scattering in gastric c.pdf | 2.45 MB | Adobe PDF | OPEN | Published | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.