epithelial-mesenchymal transition
Definition: Conversion from an epithelial to a mesenchymal phenotype, which is a normal process of embryonic development. In carcinomas, this transformation results in altered cell morphology, the expression of mesenchymal proteins and increased invasiveness.
SRC and FAK
SRC kinase controls cellular adhesions, including cadherin-based intercellular adhesions and integrin-mediated cell-matrix adhesions.
In epithelial cells, SRC activation, or increased signalling from migratory growth factor receptors via SRC, induces an adhesion switch that enhances dynamic cell-matrix adhesions and migratory capacity while suppressing intercellular contact.
Moreover, SRC and the associated tyrosine kinase FAK are at the heart of the recently identified crosstalk between integrin- and cadherin-mediated adhesions of epithelial cells, particularly during the epithelial-to-mesenchymal transition.
EMTs in tumors
Epithelial-mesenchymal transitions (EMTs) occur as key steps during embryonic morphogenesis, and are now implicated in the progression of primary tumors towards metastases. Recent advances have fostered a more detailed understanding of molecular mechanisms and networks governing EMT in tumor progression.
Besides TGFbeta and RTK/Ras signaling, autocrine factors and Wnt-, Notch-, Hedgehog- and NF-kappaB-dependent pathways were found to contribute to EMT.
Repression of E-cadherin by transcriptional regulators such as Snail or Twist emerges as one critical step driving EMT, and this stage is currently being molecularly linked with many of the new players.
Increasing evidence suggests that EMT plays a specific role in the migration of cells from a primary tumor into the circulation and may provide a rationale for developing more effective cancer therapies.
References
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