INTEGRIN-LINKED KINASE ACTIVITY IS ASSOCIATED WITH PROGRESSIVE BEHAVIOR OF PANCREATIC CANCER

Abstract

Background: Cancer cell adhesion and invasion into extracellular matrix (ECM) proteins are regulated by β1-integrin and integrin-linked kinase (ILK) activity. We sought to determine the role of ILK activity in pancreatic cancer cells. Materials and Methods: Expression of the β1-integrin and ILK in 4 human pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, SW1990) was determined by RT-PCR and Western blot. The MAPK signaling pathway and ILK kinase activity were examined with immunoblotting. The role of the ILK activity on signaling pathways and the pancreatic cancer cell invasion was determined by cDNA constructs transfection studies. Invasion was examined using a Matrigel double-chamber assay. Using immunohistochemical analysis, the relationship between the ILK expression and clinicopathological features of pancreatic cancer patients were investigated. Results: All four pancreatic cancer cell lines expressed β1-integrin and ILK both in mRNA and protein levels. Alteration of ILK kinase activity controlled p38 MAPK phosphorylation with subsequent regulation of pancreatic cancer cell adhesion and invasion. Overexpressed ILK enhances the p38 MAPK phosphorylation strongly through GSK-3 activation which promotes aggressive capabilities of pancreatic cancer cells. In contrast, knockdown of ILK kinase activity inhibits the activation of MAPK pathway via inhibition of GSK-3 phosphorylation. In immunohistochemical analysis, statistically significant association between strong expression of ILK and poor prognosis of pancreatic cancer patients were observed. Conclusions: Our results suggest that ILK is involved with aggressive capability in pancreatic cancer and that these regulations can be helpful to understand biological processes for better translational treatment for pancreatic cancer patients.