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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.

Mesenchymal‐transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT 3 and WNT 5B