title: Clinical significance and biological roles of CRKL in human bladder carcinoma.
abstract: CRKL encodes an adaptor protein that has been recently reported to be overexpressed in various cancers and associate with the malignant behavior of cancer cells. However, the expression pattern of CRKL protein and its clinical significance in human bladder cancer have not been well characterized to date. In the present study, CRKL expression was analyzed in 82 archived bladder cancer specimens using immunohistochemistry, and the correlations between CRKL expression and clinicopathological parameters were evaluated. We found that CRKL was overexpressed in 31 of 82 (37.8%) bladder cancer specimens. A significant association was observed between CRKL overexpression and tumor status (p = 0.019). To further explore the biological functions of CRKL in bladder cancer, we overexpressed CRKL in BIU-87 and 5637 cell lines. Using CCK8 assay and colony formation assay, we showed that CRKL upregulation increased cell proliferation. In addition, transwell assay showed that CRKL could also facilitate invasion. Further study demonstrated that CRKL upregulation increased cyclin D1 expression and ERK phosphorylation. In conclusion, CRKL is overexpressed in bladder cancer and regulates malignant cell growth and invasion, which makes CRKL a candidate therapeutic target for bladder cancer.
authors.affiliation: Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.forename: Lan
authors.initials: L
authors.lastname: Luan
authors.forename: Zhenqun
authors.initials: Z
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000032:analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D010766:Phosphorylation; D001743:Urinary Bladder / Q000737:chemistry; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C530104:CCND1 protein, human; C082869:CRKL protein; D009687:Nuclear Proteins; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases