title: Inhibition of focal adhesion kinase induces apoptosis in bladder cancer cells via Src and the phosphatidylinositol 3-kinase/Akt pathway.
abstract: Focal adhesion kinase (FAK) is a 125-kDa, cytosolic, non-receptor, protein tyrosine kinase localized at focal adhesions that can be activated by multiple inputs and in different manners. FAK is implicated in signaling pathways regulating cell movement, invasion, survival, gene expression and cancer stem cell self-renewal. The aim of the present study was to investigate whether FAK plays a role in the apoptosis of bladder cancer cells. The study employedin situdeoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and Annexin V labeling flow cytometry. It was found that both the knockdown of FAK and the suppression of FAK phosphorylation were able to induce apoptosis in bladder cancer cells. Caspase-3 was activated during the apoptosis induced by the suppression of FAK phosphorylation. Src was involved in FAK-regulated apoptosis in bladder cancer cells, while the suppression of Src phosphorylation was able to inhibit FAK tyrosine phosphorylation and induce apoptosis. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt signaling was inhibited via the suppression of FAK tyrosine phosphorylation. Conversely, the expression of neither the general nor the tyrosine-phosphorylated FAK was regulated by inhibiting PI3K/Akt, which suggested that PI3K/Akt acted downstream of FAK to regulate apoptosis in bladder cancer cells. These findings indicate the presence of a mechanism of apoptosis involving FAK-mediated oncogenic signaling. FAK may function as an important regulator of extracellular signaling-mediated apoptosis in bladder cancer and be used as a novel therapeutic target in the treatment of the condition.
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Debo
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Surgery, The Jiujiang Traditional Chinese Medicine Hospital, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Gynecologic Oncology, Women's Reproductive Health Key Laboratory of Zhejiang, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: N I
authors.initials: NI
authors.lastname: Sima
keywords: Src; apoptosis; bladder cancer; focal adhesion kinase; phosphatidylinositol 3-kinase/Akt