Integrin-linked kinase regulates E-cadherin expression by means of the transcription factor Snail

The integrin-linked kinase (ILK) is an ankyrin repeat containing serine–threonine protein kinase, which can interact with the cytoplasmic domains of integrin β₁ and β₃ subunits and can be activated by integrins and growth factors. When overexpressed in epithelial cells, ILK inhibits E-cadherin expression, causing an epithelial to mesenchymal transformation. I demonstrate that ILK represses E-cadherin expression by stimulating the expression of Snail, a transcription factor that binds and represses the E-cadherin promoter. Inhibition of ILK in colon cancer cells with a highly selective ILK inhibitor, or dominant-negative ILK, resulted in the inhibition of Snail expression and a concomitant stimulation of expression of E-cadherin. Inhibition of ILK also suppressed β-catenin/TCF transcriptional activity in APC^−/− colon cancer cells and induced cellular growth arrest as well as growth inhibition of human colon tumors xenografted into SCID mice. Inhibition of ILK may reverse the frequent epithelial-to-mesenchymal transformation associated with tumor invasion and metastasis. ILK is a promising target for the control of cancer progression.