MOLECULAR MECHANISMS LEADING TO LOSS OF DIFFERENTIATION AND GAIN OF INVASIVENESS IN EPITHELIAL-CELLS

It has been realized for some time that the loss of epithelial differe ntiation in carcinomas, which is accompanied by higher mobility and in vasiveness of the tumor cells, is a consequence of reduced intercellul ar adhesion. A variety of recent reports have indicated that the prima ry cause for the `scattering' of the cells in invasive carcinomas is a loss of the integrity of intercellular junctions. Thus, defects in ex pression or structure of several components of the epithelial adherens junctions (e.g. E-cadherin, alpha-catenin) can occur, and our increas ed knowledge about the molecules of the junctions allows an explanatio n of these defects in molecular terms in some of the cases. Furthermor e, tyrosine phosphorylation of junctional components (e.g. beta-cateni n) appears to play a role in the assembly and disassembly of cell-cell contacts. Some of the effecters of epithelial junction formation are tyrosine protein kinases, e.g. the scatter factor/hepatocyte growth fa ctor receptor c-Met, the FGF receptors and the pp60(s7c) kinase. The i mportance of tyrosine phosphorylation in junctions during tumor develo pment is becoming increasingly evident.