Epithelial-to-mesenchymal transition (“EMT”) is a complex dynamic process that occurs during embryonic development for reprogramming of epithelial cells. Downregulation of E-cadherin, which occurs during EMT, results in the loss of homotypic adhesion. Reactivation of EMT during adult life has been associated with various pathological conditions. For example, EMT promotes the detachment of cancer cells from the primary tumor and facilitates migration through the acquisition of stem cell like properties, including loss of cellular polarity and adhesion. Metastasis and resistance to systemic therapies pose major clinical challenges to the treatment of breast and other cancers. Identification of tumor-coded genes and determining how these genes contribute to progression of the disease is important for developing new therapeutic strategies.
Although the significance of EMT in development of drug resistance, metastasis and stem cell-like characteristics of cancer cells has become evident, the mechanisms/pathways that lead to the induction of EMT/stem cell phenotype remain elusive. Delineation of these pathways could offer novel and promising therapeutic targets for treating drug resistant and metastatic tumors, which account for more than 90% cancer related death. To date, however, the specific inducers of EMT/stem cells are not known. Targets for inhibiting the expression of these phenotypes could produce cancer therapies that alone or in combination with existing drugs combat drug resistance.