Rac regulates the stability of the adherens junction and its components, thus affecting epithelial cell...

We have previously reported that activated rac (V12rac) can bring about hypertransformation of ras-transformed epithelial cells, which can be suppressed by the dominant negative form of rac (N17rac). Starting with primary epithelial cells, a series of cell lines expressing wild type (WT) or mutated forms of ras or rac were generated and analysed for their adhesive function and expression and association of adherens junction (AJ) proteins. Normal, primary epithelial cells were self-adhesive and expressed AJs that were very stable. The expression of constitutively active ras resulted in a decrease in, but not loss of, cell-cell adhesion, with concomitantly decreased stability of AJ components. This was extremely exacerbated by the co-expression of constitutively activate rac, but was suppressed by dominant negative rac, which resulted in increased cell-cell adhesion and extremely stable AJs. alpha-catenin also failed to associate with E-cadherin-beta-catenin complexes in cells expressing V12rac. Expression of V12rac resulted in the loss of epithelial morphology. The extent of transformation of each cell type corresponded to the stability of the respective AJ complexes. Thus, rac seems to be involved in regulating the stability of AJs, which promote epithelial cell differentiation, and consequently, modulating tumor progression.