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PI3K/Akt-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration
- Source :
-
Cellular Signalling . Feb2013, Vol. 25 Issue 2, p447-456. 10p. - Publication Year :
- 2013
-
Abstract
- Abstract: 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 100ng/mL, via enhancing phosphorylation of PI3K/Akt and GSK3β and activating RhoA. Pharmaceutical inhibition of PI3K with LY294002 or Akt siRNA significantly decreased Wnt5a-induced GSK3β phosphorylation and consequently cell migration. Additionally, GSK3β siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Analogously, pre-treatment with LiCl, which induced phosphorylation of GSK3β 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/GSK3β/RhoA signaling pathway. These findings could provide a rationale for designing new therapy targeting gastric cancer metastasis. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 08986568
- Volume :
- 25
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cellular Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 84476323
- Full Text :
- https://doi.org/10.1016/j.cellsig.2012.10.012