title: Focal adhesion kinases crucially regulate TGFβ-induced migration and invasion of bladder cancer cells via Src kinase and E-cadherin.
abstract: Focal adhesion kinase (FAK) is a non-receptor protein-tyrosine kinase that is triggered off by special extracellular signals such as some growth factors and integrins. FAK is found in cell-matrix attachment sites and implicated in cell migration, invasion, movement, gene expression, survival and apoptosis. In this study, we aimed to investigate whether FAK plays a role in invasion and migration of bladder cancer cells. Using an FAK-specific small interfering RNA (siRNA) and an FAK inhibitor PF-228, we found that inhibition of FAK tyrosine phosphorylation or knockdown of FAK suppressed invasion and migration of bladder cancer cells. Src is an important mediator of FAK-regulated migratory and invasive activity. Tyrosine phosphorylation of Src and FAK is mutually dependent and plays a key role in transforming growth factor beta (TGFβ)-induced invasion and migration. E-cadherin acts downstream of FAK and is a critical negative regulator in FAK-regulated invasion and migration of bladder cancer cells. These findings imply that FAK is involved in oncogenic signaling of invasion and migration, which can be a novel therapeutic target to treat patients with bladder cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang.
authors.forename: De-Bo
authors.initials: DB
authors.lastname: Kong
authors.affiliation: Department of Surgery, The Jiujiang Traditional Chinese Medicine Hospital, Jiujiang, Jiangxi.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Women's Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors.forename: Ni
authors.initials: N
authors.lastname: Sima
keywords: E-cadherin; Src kinase; bladder cancer; focal adhesion kinase; migration/invasion; transforming growth factor beta