Journal
GENES TO CELLS
Volume 16, Issue 3, Pages 304-315Publisher
WILEY
DOI: 10.1111/j.1365-2443.2011.01487.x
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [23650595] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available