Figure 4. FIGURE 4: Reduced schematic of EpCAM regulation in the context of EMT.

Stimulation of tyrosine kinase receptors via TGF-β1 or EGF is leading to ERK2 activation and suppresses EPCAM mRNA expression indirectly through activation of EMT-associated transcription factors (TF) like SNAI1, SNAI2, TWIST1 and ZEB1. The EpCAM protein on the other hand could also contribute to the regulation of EMT by suppressing ERK2 activity. The soluble EpEX-fragment is acting as an EGF competitor for EGFR, counteracted EMT via inhibiting of the EMTTF (Snail, ZEB1, and Slug) which leads to activation of EPCAM expression. For detailed review, see references [42, 91, 92].