Implications of Mesenchymal Cells in Cancer Stem Cell Populations: Relevance to EMT

The epithelial to mesenchymal transition (EMT) generates tumor cells having stem cell characteristics with phenotypes similar to cancer stem cells (CSCs). Evidence suggests CSCs are in an intermediate state of EMT expressing reduced levels of E-cadherin and exhibiting mesenchymal features including invasiveness associated with metastasis. These findings suggest mechanisms regulating EMT and stemness are closely integrated. Recent reports from multiple laboratories have identified novel mechanisms regulating EMT and stemness involving epigenetics, microenvironment, and dedifferentiation. Circulating tumor cells (CTCs) have also been shown to exhibit features of EMT, but it is unclear what fraction has CSCs properties. EMT characteristics of both CSCs and CTCs are associated with resistance to current clinical treatments, indicating therapies targeting the CSC in addition to the more differentiated tumor cells are required for durable responses. Thus, EMT characteristics of CTCs may prove useful biomarkers for effective therapies for many cancers.