Induction
Several oncogenic pathways (peptide growth factors, Src, Ras, Ets, integrin, Wnt/beta-catenin and Notch) may 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. Interestingly, Slug triggers the steps of desmosomal disruption, cell spreading, and partial separation at cell–cell borders, which comprise the first and necessary phase of the EMT process. On the other hand, Slug cannot trigger the second phase, which includes the induction of cell motility, repression of the cytokeratin expression, and activation of vimentin expression.
Snail and Slug are known to regulate the expression of isoforms of another transcription factor p63 that is required for proper development of epithelial structures. The altered expression of p63 isoforms reduced cell–cell adhesion and increased the migratory properties of cancer cells. The p63 factor is involved in inhibiting EMT and reduction of certain p63 isoforms may be important in the development of epithelial cancers. Some of them are known to regulate the expression of cytokeratins.
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 possibly 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.
As cells assume a more mesenchymal phenotype, expression of molecules such as osteopontin and type 1 collagen are increased.
Read more about this topic: Epithelial-mesenchymal Transition
Famous quotes containing the word induction:
“One might get the impression that I recommend a new methodology which replaces induction by counterinduction and uses a multiplicity of theories, metaphysical views, fairy tales, instead of the customary pair theory/observation. This impression would certainly be mistaken. My intention is not to replace one set of general rules by another such set: my intention is rather to convince the reader that all methodologies, even the most obvious ones, have their limits.”
—Paul Feyerabend (1924–1994)
“They relieve and recommend each other, and the sanity of society is a balance of a thousand insanities. She punishes abstractionists, and will only forgive an induction which is rare and casual.”
—Ralph Waldo Emerson (1803–1882)