Fig. 2.

Schematic representation of cell signalling events modulated by increased N-cadherin expression in the context of cell migration. a In addition to mediating cellular aggregation, N-cadherin may facilitate the collective migration of tumour cells by excluding focal adhesions and Rac1 activity, and promoting RhoA activity, at sites of N-cadherin-mediated cell-cell contact. The asymmetric distribution of N-cadherin adhesive complexes polarises integrin function and Rac1 activity towards the free edges of cells, thereby directing focal adhesion and lamellipodia formation away from the cell cluster and promoting cell migration. Similar to Rac1, N-cadherin-mediated cell-cell adhesion promotes cdc42 activity at the free edges of cells, resulting in filipodia formation. b Functional interaction between the extracellular domains of N-cadherin and FGFR-1 potentiates FGF-2-activated FGFR-1 signalling by attenuating ligand-induced receptor internalisation. The resulting augmentation of down-stream MEK/ERK and PI3K/Akt signalling promotes the metastatic behaviour of cancer cells by increasing the production of invasion-facilitating molecules such as matrix metalloproteinases (MMPs). c N-cadherin-mediated adhesive complexes and Wnt/β-catenin signalling are thought to compete for the same cellular pool of β-catenin. While N-cadherin sequesters β-catenin from the nucleus, the N-cadherin adhesive complex provides a reservoir of β-catenin which, upon Wnt activation, becomes available for nuclear translocation and TCF/LEF-mediated gene transcription (e.g. CD44 and MMP genes), resulting in the loss of N-cadherin-mediated cellular adhesion in cancer cells