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
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