Contribution of Epithelial-Mesenchymal Transition Process to Plasticity of Cancer Stem Cells

The epithelial-mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is responsible for metastasis, relapse, and chemoresistance. Molecular links between EMT and cancer stem cells (CSCs) have emerged, suggesting that EMT programs play important roles in expressing CSC-like properties. Recently, some results have linked mesenchymal-epithelial transition (MET) and stem cell-like traits, challenging the recognition of the relationship between EMT and CSCs. The prevailing opinion suggests that EMT-transcription factors (EMT-TFs) need to be downregulated to convert mesenchymal cells into an epithelial phenotype, thereby increasing proliferation to promote metastatic tumor formation. However, the downregulation of EMT-TFs cannot induce stemness independently; the regulation of stem cell characteristics is independent of the EMT program. Importantly, the genetic and epigenetic mechanisms that regulate the activation of MET and cancer stem cells remain unclear and are under intensive investigation. Understanding the biology of CSCs plasticity, the MET program, and their implications in therapeutic targets may provide new opportunities for therapeutic intervention.