Epithelial-mesenchymal transition as a fundamental mechanism underlying the cancer phenotype.

Epithelial-mesenchymal transition (EMT) is a complex process involved in embryonic development, wound healing and carcinogenesis. During this process, epithelial cells lose their defining characteristics and acquire mesenchymal properties: loss of cell-cell adhesion; increased motility and invasiveness; resistance to apoptosis and changes in cellular morphology. EMT has been implicated as a driver of metastasis and tumour invasion, as this process allows cells to detach from their niche and migrate through blood and lymphatic vessels to invade different organs. This transition involves a diverse range of transcription factors, including Twist, Snail and ZEB1, and downstream transcriptional targets, including E-cadherin, β-catenin, fibronectin and vimentin. Recent evidence indicates that cancer stem cells are required for metastatic tumours to become established at a distant site, and that cancer cells undergoing EMT may develop stem-cell characteristics as well as increased invasive potential. The role of EMT in cancer biology is newly emerging in the human field, and to date very little has been done in veterinary medicine. EMT may therefore be an important molecular determinant of tumour metastasis, and further understanding of this process may lead to novel drug targets to be exploited in both veterinary and human medicine.