Epithelial Plasticity in Tumor Progression and Wound Repair: Potential Therapeutic Targets in the Stromal Microenvironment

Epithelial transdifferentiation or cellular “plasticity” refers to a morphogenetic switch resulting in loss of normal epithelial properties, again in the expression of genes is generally restricted to the mesenchymal lineage and acquisition of a migratory phenotype. Essential during development and organogenesis (i.e., embryonic patterning), epithelial plasticity is relatively limited in the adult organism, occurring during wound healing and regenerative repair or, more typically, in tissue fibrosis and tumor metastasis. The temporal and spatial regulation of the plastic phenotype is likely a collective response to specific growth factors and cues from the extracellular environment. Among the various inducers of cellular transdifferentiation, members of the transforming growth factor-β are, perhaps, the most prominent, impacting both the emergence and persistence of the plastic restructuring.