(A) Schematic of FGFR2 alternative splicing during EMT. Isoform
switching from the epithelial FGFR2-IIIb to the mesenchymal FGFR2-IIIc changes
the structure of an immuoglobin-like domain to enhance the binding affinity to
FGF.
(B) Schematic of CD44 alternative splicing during EMT. Epithelial
isoform CD44v has a longer extracellular stem region than mesenchymal isoform
CD44s. The two isoforms activate Ras/MAPK pathway and PI3K/Akt,
PDGFRβ/Stat3 pathways, respectively.
(C) Schematic of Ron alternative splicing during EMT. The mesenchymal
isoform ∆Ron lacks a 49-amino acid region in the extracellular domain of
the β-subunit and is constitutively active.
(D) Schematic of Rac1 alternative splicing during EMT. The mesenchymal
Rac1b isoform is in the GTP-bound active conformation, generating ROS and
induces SNAI1 expression.
(E) Schematic of p120-catenin (CTNND1) splicing during EMT. Mesenchymal
isoform 1 is the longest isoform that contains a coiled-coil domain and a
regulatory domain, inhibiting RhoA activity and promoting Rac1 activity. The
epithelial isoform 4 lacks both domains and promotes RhoA activity.