Epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) is a program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation.

Several oncogenic pathways (peptide growth factors, Src, Ras, Ets, integrin, Wnt/beta-catenin and Notch) induce EMT. In particular, Ras-MAPK has been shown to activate two related transcription factors known as Snail and Slug. Both of these proteins are transcriptional repressors of E-cadherin and their expression induces EMT. Recently, activation of the phosphatidylinositol 3' kinase (PI3K)/AKT axis is emerging as a central feature of EMT.

Twist, another transcription factor, has also been shown to induce EMT, and is also implicated in the regulation of metastasis. Expression of FOXC2, an important player during embryonic development has been shown to induce EMT and regulate metastasis. Moreover, expression of FOXC2 is induced when epithelial cells undergo EMT by Snail, Twist, Goosecoid, and TGF-beta 1.

Initiation of metastasis involves invasion, which has many phenotypic similarities to EMT, including a loss of cell-cell adhesion mediated by E-cadherin repression and an increase in cell mobility.

EMT is a characteristic feature of cells undergoing proliferation. Cells expanding in-vitro, like beta cells- and epithelial phenotype, of the pancreas, assume mesenchymal phenotype.

Sources

• Vernon, A., and LaBonne, C. (2004). "Tumor metastasis: a new twist on epithelial-mesenchymal transitions". Current Biology 14 719–21.
• Yang, J., Mani, S., Donaher, J., Ramaswamy, S., Itzkyson, R., Come, C., Savagner, P., Gitelman, I., Richardson, A., and Weinberg, R. (2004). "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis". Cell 117 927–39. .
• Sendurai A. Mani, Jing Yang, Mary Brooks, Gunda Schwaninger, Alicia Zhou, Naoyuki Miura, Jeffery L. Kutok, Kimberly Hartwell, Andrea L. Richardson, and Robert A. Weinberg (2007). "Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers.". Proceedings of the National Academy of Sciences 104 (24): 10069–74.