Open AccessMesenchymal‐transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT 3 and WNT 5B
Author(s) -
Kato Shinichiro,
Hayakawa Yoshihiro,
Sakurai Hiroaki,
Saiki Ikuo,
Yokoyama Satoru
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12336
Subject(s) - mesenchymal stem cell , cancer cell , wnt signaling pathway , cancer , epithelial–mesenchymal transition , tumor microenvironment , cancer research , biology , secretion , metastasis , microbiology and biotechnology , tumor cells , signal transduction , endocrinology , genetics
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 WNT 3 and WNT 5B 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.