PI3K/Akt-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration

被引：91

作者：

Liu, Jiaojing ^{[1
,2
]}

Zhang, Yujie ^{[2
]}

Xu, Rui ^{[3
]}

Du, Jun ^{[1
,3
]}

Hu, Zhenzhen ^{[1
]}

Yang, Ling ^{[4
]}

Chen, Yongchang ^{[5
]}

Zhu, Yichao ^{[1
,3
]}

Gu, Luo ^{[1
,3
]}

机构：

[1] Nanjing Med Univ, Ctr Canc, Nanjing 210029, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Dept Biochem & Mol Biol, Nanjing 210029, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Dept Physiol, Nanjing 210029, Jiangsu, Peoples R China

[4] Suzhou Univ, Affiliated Hosp 3, Dept Cardiol, Changzhou 213003, Jiangsu, Peoples R China

[5] Jiangsu Univ, Dept Physiol, Zhenjiang 212013, Jiangsu, Peoples R China

来源：

CELLULAR SIGNALLING | 2013年 / 25卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Wnt5a; Gastric cancer; Migration; PI3K/Akt; GSK3; beta; RhoA; SIGNALING PATHWAY; WNT-5A PROTEIN; EXPRESSION; SURVIVAL; METASTASIS; MELANOMA; ADHESION; INVASION; 3-KINASE;

D O I：

10.1016/j.cellsig.2012.10.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wnt5a, a non-transforming Wnt family member, plays complicated roles in oncogenesis and cancer metastasis. However, Wnt5a signaling in gastric cancer progression remains poorly defined. In this study, we found that Wnt5a dose-dependently stimulated the migration of human gastric cancer cells (SGC-7901), with the maximal effect at 100 ng/mL, via enhancing phosphorylation of PI3K/Akt and GSK3 beta and activating RhoA. Pharmaceutical inhibition of FISK with LY294002 or Akt siRNA significantly decreased Wnt5a-induced GSK3 beta phosphorylation and consequently cell migration. Additionally, GSM beta siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Analogously, pre-treatment with LiCl, which induced phosphorylation of GSK3 beta at Ser9, increased Wnt5a-induced cell migration. Finally, ectopic expression of dominant negative RhoA (N19) suppressed Wnt5a-induced cell migration. Taken together, we demonstrated for the first time that Wnt5a promoted gastric cancer cell migration via the PI3K/Akt/GSK3 beta/RhoA signaling pathway. These findings could provide a rationale for designing new therapy targeting gastric cancer metastasis. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.

引用

页码：447 / 456

页数：10

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