ILK overexpression in human hepatocellular carcinoma and liver cirrhosis correlates with activation of Akt.

Hepatocellular carcinoma (HCC) is one of the most common life-threatening malignancies in the world. The molecular mechanisms leading to the development of HCC are complex and only recently have they begun to be clarified. Integrin linked-kinase (ILK), a multifunctional signaling and scaffold protein of focal adhesion plaques, has been implicated in the pathogenesis of several human malignancies. In the current study the expression of ILK, beta-catenin and E-cadherin and the phosphorylation of Akt were studied by immunohistochemistry in 69 human HCCs and adjacent normal and cirrhotic liver parenchyma. ILK and phosphorylated-Akt (p-Akt) immunostaining was observed in 100 and 79.7% of HCCs, respectively, and their protein levels correlated significantly. Activation of beta-catenin and downregulation of E-cadherin were frequently observed in HCC, but they were not related to ILK expression. A strong correlation between ILK expression and phosphorylation of Akt was also observed in cirrhotic liver. Moreover, downregulation of E-cadherin and membranous beta-catenin were found in cirrhotic tissue suggesting their involvement in the liver tissue remodeling observed in cirrhosis. Our results indicate that ILK overexpression during liver oncogenesis and cirrhosis correlates with activation of Akt but not with other conventional ILK targets.