Antagonists of the N-cadherin/Fibroblast growth factor receptor tyrosine kinase complex.

This review describes similarities between the biological actions of cell adhesion molecule antagonists and pan-growth factor receptor tyrosine kinase (GF-RTK) antagonists. In particular, the biological consequences of the interaction between the cell adhesion molecule, neural (N)-cadherin (CDH2) and the fibroblast GF-RTK (FGF-RTK) are discussed. Intercellular adhesion mediated by N-cadherin stimulates FGF-RTK activity triggering intracellular signaling pathways (e.g. PI3/Akt/mTOR pathway) that regulate various morphogenetic processes (e.g. apoptosis). Antagonists of either N-cadherin or GF-RTKs modulate these processes. N-cadherin antagonists can be regarded as a previously unappreciated class of FGF-RTK inhibitors. These antagonists, similar to GF-RTK antagonists should be capable of serving as therapeutics for treating a variety of fibrotic diseases and cancers.