EGFR Signalling in EMT - Therapeutic Strategies in Cancer Biology and Pathology - page 56

EGFR TGF- β

?

Slug/Snail ↑ Akt ERK1/2 CD44 TM4SF5

E-Cadherin MMP

EMT

Figure 8.1 The postulated pathways of the induction of EMT by EGFR activation by its own
ligand and TGF-β. TGF-β-mediated activation of EGFR may involve the proteinase ADAM 17,
inhibition of which suppresses Akt activation (not shown here), but the precise mode of action
needs elucidation. MiRNAs play a substantial role in the regulation of signalling by EGFR
family. This is not shown here nor discussed in this section since this topic has been reviewed
in detail in another location (see pp. 5-24 and Figures 3.4-3.7).

Overall there is overwhelming evidence that EGF/EGFR activates EMT, although
the modes of initiation of EMT are yet to be fully elucidated. Nevertheless there are
very clear leads that can be followed up, especially in relation to the interactions of
EGFR with cell membrane determinants of invasion and adhesive function and the
signalling systems that might be relevant in the context of EGF/EGFR-mediated
changes in cell behaviour ( Figure 8.1 ).