Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B
Article first published online: 29 JAN 2014
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 3, pages 281–289, March 2014
How to Cite
Cancer Sci 105 (2014) 281–289
Grants-in-aid for Challenging Exploratory Research (24659348) and Grant-in-aid for Young Scientists (B) (24700971) from Ministry of Education, Culture, Sports, Science, and Technology, Japan. Grant-in-Aid for JSPS Fellows (DC2) (2510159) from Japan Society for the Promotion of Science, Japan.
- Issue published online: 6 MAR 2014
- Article first published online: 29 JAN 2014
- Accepted manuscript online: 17 DEC 2013 09:17AM EST
- Manuscript Accepted: 12 DEC 2013
- Manuscript Revised: 10 DEC 2013
- Manuscript Received: 8 NOV 2013
- Ministry of Education, Culture, Sports, Science, and Technology, Japan. Grant Numbers: 24659348, 24700971
- Japan Society for the Promotion of Science, Japan. Grant Number: 2510159
- epithelial-to-mesenchymal transition;
- metastasis WNT
Although the heterogeneities of epithelial and mesenchymal-transitioned cancer cells are often observed within the tumor microenvironment, the biological significance of the interaction between epithelial cancer cells and mesenchymal-transitioned cancer cells is not yet understood. In this study, we show that the mesenchymal-transitioned cancer cells instigate the invasive ability and metastatic potential of the neighboring epithelial cancer cells in vitro and in vivo. We identify WNT3 and WNT5B as critical factors secreted from Transforming growth factor-induced mesenchymal cancer cells for instigating the epithelial cancer cell invasion along with the induction of secondary EMT phenotype. These results shed light on the significance of cancer heterogeneity and the interaction between epithelial and mesenchymal-transitioned cancer cells within the tumor microenvironment in promoting metastatic disease through the WNT-dependent mechanism.