期刊
CELLULAR SIGNALLING
卷 25, 期 2, 页码 447-456出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.10.012
关键词
Wnt5a; Gastric cancer; Migration; PI3K/Akt; GSK3 beta; RhoA
类别
资金
- National Natural Science Foundation of China [81172002, 81101999]
- Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University
- College Graduates Research and Innovation Program of Jiangsu Province [CXZZ12_0556]
- Natural Science Foundation of Jiangsu Province [BK2012893]
- Postdoctoral Science Foundation of China [2011M501254, 2012T50484]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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.
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