Revisiting epithelial‐mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness

Epithelial‐mesenchymal transition (EMT) is an important process in embryonic development, fibrosis, and cancer metastasis. During cancer progression, the activation of EMT permits cancer cells to acquire migratory, invasive, and stem‐like properties. A growing body of evidence supports the critical link between EMT and cancer stemness. However, contradictory results have indicated that the inhibition of EMT also promotes cancer stemness, and that mesenchymal‐epithelial transition, the reverse process of EMT, is associated with the tumor‐initiating ability required for metastatic colonization. The concept of ‘intermediate‐state EMT’ provides a possible explanation for this conflicting evidence. In addition, recent studies have indicated that the appearance of ‘hybrid’ epithelial‐mesenchymal cells is favorable for the establishment of metastasis. In summary, dynamic changes or plasticity between the epithelial and the mesenchymal states rather than a fixed phenotype is more likely to occur in tumors in the clinical setting. Further studies aimed at validating and consolidating the concept of intermediate‐state EMT and hybrid tumors are needed for the establishment of a comprehensive profile of cancer metastasis.