%0 Journal Article
%T Activation of focal adhesion kinase enhances the adhesion and invasion of pancreatic cancer cells via extracellular signal-regulated kinase-1/2 signaling pathway activation
%A Hirozumi Sawai
%A Yuji Okada
%A Hitoshi Funahashi
%A Yoichi Matsuo
%A Hiroki Takahashi
%A Hiromitsu Takeyama
%A Tadao Manabe
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-37
%X In immunoblotting analysis, all three pancreatic cancer cell lines (AsPC-1, BxPC-3, and Capan-2) expressed the protein of FAK and ¦Â1 integrin. Enhancement of FAK protein association with ¦Â1 integrin when cells were plated on Coll IV was more increased by stimulation with IL-1¦Á. Preincubation with anti-¦Â1 integrin antibody and FAK siRNA transfection inhibited the association of FAK with ¦Â1 integrin of pancreatic cancer cells. FAK phosphorylation was observed by adhesion to Coll IV, furthermore, stronger FAK phosphorylation was observed by stimulation with IL-1¦Á of pancreatic cancer cells adhered to Coll IV in time-dependent manner. Genistein, a tyrosine kinase inhibitor, markedly inhibited the FAK phosphorylation. IL-1¦Á stimulation and Coll IV adhesion enhanced the activation of Ras, as evidenced by the increased Ras-GTP levels in pancreatic cancer cells. Activation of Ras correlated with the phosphorylation of ERK. While not statistical affecting the apoptosis of pancreatic cancer cells, IL-1¦Á-induced adhesion and invasion on Coll IV were inhibited with FAK gene silencing by siRNA, ¦Â1 integrin blocking, and inhibition of FAK phosphorylation. PD98059, a MEK inhibitor, also inhibited IL-1¦Á-induced enhancement of adhesion and invasion in pancreatic cancer cells.Our results demonstrated that activation of FAK is involved with the aggressive capability in pancreatic cancer through Ras/ERK signaling pathway. Based on our results, we suggest that the modification of IL-1, FAK, and integrins functions might be a novel therapeutic approach to aggressive spread of pancreatic cancer.Integrin binding to extracellular matrix (ECM) protein or integrin crosslinking increases tyrosine phosphorylation of focal adhesion kinase (FAK) [1,2]. FAK is a tyrosine kinase considered a central molecule in integrin-mediated signaling, and it is involved in cellular motility and protection against apoptosis [3-7]. The carboxyl-terminal tyrosine residue (tyr397) of FAK, constitutes a major site
%U http://www.molecular-cancer.com/content/4/1/37