Involvement of Rho GAP GRAF1 in maintenance of epithelial phenotype

Here, we studied the role of a Rho GAP protein GRAF1 ( G TPase R egulator A ssociated with F ocal adhesion kinase- 1 ) in the regulation of the epithelial phenotype in cells of breast derived, non-malignant, MCF10A cell line.

GRAF1 was shown to be localized to cell-cell junctions, and its depletion resulted in accelerated cell migration velocity, elongation of the cells and cell colonies, impaired monolayer integrity and significant disruption of desmosomes with a loss of associated keratin filaments. These processes were accompanied by formation of larger focal adhesions, an increased number of contractile actin stress fibers, reduction in epithelial markers and increase in mesenchymal markers such as epithelial-mesenchymal transition (EMT)-specific transcription factors Snail-1 and Snail-2, as well as N-cadherin, and vimentin.