Key Factors In EMT: Critical Process In Breast Cancer Malignancy

Epithelial Mesenchymal Transition (EMT) is an event of gaining mesenchymal features by epithelialcells. It has an important role in invasiveness and migration of cancerous cells, besides to tissuedevelopment and wound healing. These properties can lead to metastasis and drug resistancewhich are the main reasons of cancer relapse and death. Although there are advanced therapeuticmethods against breast cancer, metastasis of epithelial breast cancer cells complicates theefficiency of treatment causing low survival rate of patients. E-cadherin expression which has keyrole in cell-cell adhesion decreases during EMT and the cells lose their junctions and can migrate toother sites. Other cell adhesion molecules level such as claudin and occluding decrease in cellmembrane. In contrast, expression of mesenchymal genes such as N-cadherin, vimentin andfibronectin increase. A variety of intracellular factors including twist which is a member of basichelix-loop-helix transcription factor, and snail1, snail2 (slug), ZEB1, ZEB2 which can bind to E-boxelement of cell adhesion genes and regulate EMT. These EMT- related transcription factors areaffected by different signaling cascades such as TGF-β, RTKs, Wnt, and notch. All in all, this reviewarticle underlines the role of transcription factors and signaling pathways that regulate E-cadherinexpression. A comprehensive look at pathway of EMT can help us to choose effective candidategenes for targeted therapy. Moreover, it should be considered that increasing E-cadherin and othercell junction components expression lead to mesenchymal epithelial transition (MET) which isnecessary for fixation of migrated tumor cells in distant tissue. Consequently, it is important tochoose candidate gene for targeted therapy according to stage of the cancer.