Epithelial to mesenchymal transition (EMT) is a process by which cells of an epithelial phenotype dedifferentiate to a motile mesenchymal phenotype. The Epithelial cell reorganizes its actin cytoskeleton from a cortical junctional associated arrangement to form motile stress fibres, redistributes and down regulates its cell-cell contacts, loses its polarity, and upregulates mesenchymal markers such as α-smooth muscle actin (α-SMA) and vimentin . The cell also shifts its association with the basal lamina by altering the composition of its extracellular matrix (ECM) contacts and secreting matrix metalloproteinases . EMT has a role during development , chronic fibrotic disorders , and a postulated role in epithelial cancer metastasis .
Transforming growth factor beta-1 (TGF-β1) can trigger an EMT in cancer cells leading to metastasis . In order for an adenocarcinoma cell to metastasize and relocate to a different site, it must somehow lose contact with its surrounding cells, become motile and acquire the ability to manipulate the basal lamina in order to intravasate into local blood vessels or lymph system. An EMT triggered by TGF-β1 provides a hypothetical mechanism for this occurrence. It is considered important that cancerous cells lose sensitivity to the growth inhibitory effect of TGF-β1 before they undergo EMT in vivo . However loss of growth inhibition is not necessarily correlated with EMT in vitro .
Although the phenotypic characteristics of EMT are fairly well defined, the signalling pathways responsible for TGF-β1 induced EMT are not. The mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) have all been implicated despite no known direct link between TGF-β receptors and MAPK pathways [7,8,9]. In addition several other pathways have been implicated including Notch signalling (which is modulated by TGF-β signalling), β-catenin signalling, and Akt signalling [10,11,12]. A critical step in understanding both EMT and TGF-β signalling will be deciphering how these pathways are activated in response to TGF-β.
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