Table 1 Proposed Models of Pathogenesis in HDGC
No. | Pathway | Downstream Targets | Proposed Mechanism | Reference |
|---|---|---|---|---|
1. | Epithelial mesenchymal transition (EMT) | Fibronectin, FAK, and Stat3 | Initiation phase characterised by destabilisation of adherens junctions in proliferation zone and concomitant formation of SRC | [53] |
Progression phase characterised by poor differentiation, activation of c-Src kinase and induction of EMT | ||||
2. | ErbB | ErbB2, ErbB3, PI3K, p38 MAP kinase, Rac1, MEK1 | Activated ErbB2/ ErbB3 complex binds to PI3K➔ Activation of p38 MAP kinase and adherens junctions disruption via Rac1 where MEK1 pathway enhances cell–cell dissociation | |
3. | Notch | Notch-1, Bcl-2 | • ↑ Notch-1 in E-cadherin-deficient cells➔ ↑ Bcl-2➔ ↑ apoptosis resistance | [58] |