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Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of carcinoma cells following Snail-mediated epithelial-mesenchymal transition

2011; Wiley; Volume: 16; Issue: 3 Linguagem: Inglês

10.1111/j.1365-2443.2011.01487.x

1365-2443

Dayong Ren, Yasuhiro Minami, Michiru Nishita,

Tissue Engineering and Regenerative Medicine

Expression of Snail has been shown to mediate epithelial–mesenchymal transition (EMT) of epithelial cells and carcinomas, characterized by morphological alterations with disappearance and appearance of E-cadherin and vimentin, respectively. Here, we show that ectopic expression of Snail in human epidermoid carcinoma A431 cells (Snail/A431) induces the representative EMT, resulting in remarkable motile and invasive properties of the cells. Expression of Wnt5a, its receptor Ror2 and matrix metalloproteinase (MMP)-2 is induced in Snail/A431, but not in control A431 cells. Interestingly, suppressed expression of either Wnt5a or Ror2 in Snail/A431 cells results in the inhibition of in vitro cell motility and invasiveness, at least partly mediated by MMP-2, without affecting characteristics of EMT, i.e., mesenchymal morphology, and down- and up-regulations of E-cadherin and vimentin, respectively. We further show that endogenous Snail is required for sustained expression of Wnt5a, Ror2 and MMP-13 in human osteosarcoma SaOS-2 cells. The results indicate that expression of both Wnt5a and Ror2 is induced during Snail-mediated EMT or malignant progression of cancer cells and that consequently activated Wnt5a–Ror2 signaling confers highly motile and invasive properties on cancer cells. Thus, Wnt5a–Ror2 signaling can be a target of cancer therapies to prevent cancer cells from undergoing invasion and metastasis.