Molecular requirements for epithelial-mesenchymal transition during tumor progression.

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.