title: Tyrosine kinase ETK/BMX is up-regulated in bladder cancer and predicts poor prognosis in patients with cystectomy.
abstract: Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics and The Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Alan
authors.initials: A
authors.lastname: Alfano
authors.forename: Hegang
authors.initials: H
authors.lastname: Chen
authors.forename: Clara E
authors.initials: CE
authors.lastname: Magyar
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Toby C
authors.initials: TC
authors.lastname: Chai
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Qiu
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D015653:Cystectomy; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051020:bcl-X Protein; C492367:BMX protein, human; D011505:Protein-Tyrosine Kinases