title: Axlpromotes the proliferation, invasion and migration of Wilms' tumor and can be used as a prognostic factor.
abstract: OBJECTIVE
  Overexpression ofAxlhas been reported in many tumors, where it promotes tumorigenesis and progression, as well as correlates with the prognosis of different malignancies. However,Axlexpression and its function have rarely been reported in Wilms' tumor (WT). This study aimed to reveal the clinical significance ofAxlexpression in patients with WT and determine its mechanisms.
  
  
  METHODS
  We analyzed the expression ofAxland its correlations with various clinicopathological features in 72 WT tissues and 72 adjacent non-cancerous tissues by immunohistochemistry. Cox proportional hazards regression models were used to investigate the correlations betweenAxlexpression and the prognosis of WT patients. Fresh frozen samples from 20 WT patients were examined using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). In WT cell line, afterAxlknockdown by sh-Axland growth arrest-specific 6 (Gas6) stimulation, the cell proliferation, migration and invasion abilities were detected by methyl-thiazolyl-tetrazolium (MTT), clone-forming, wound-healing and transwell assays. Meanwhile, the tumor-forming ability was tested on nude mice xenograft models. Finally, the expression of several proteins in signal pathways was quantified by WB assays.
  
  
  RESULTS
  Compared with the adjacent non-cancerous tissues, the expression ofAxlwas significantly higher in WT tissues (P<0.05). High expression ofAxlwas associated with tumor recurrence or lung metastasis of WT patients and was a prognostic factor for WT patients (P<0.05). In vitro assays, the proliferation, migration and invasion of WT cells decreased withAxlknockdown and significantly increased withAxlactivation by Gas6 (P<0.05). In vivo assays, the ability of tumorigenicity in WT cells reduced dramatically afterAxlknockout (P<0.05). Moreover,PI3K-Aktpathway proteins decreased withAxlknockdown.
  
  
  CONCLUSIONS
  Our results suggest thatAxlis highly expressed in WT and is a prognostic factor, which could promote the progression of WT in vitro and in vivo. It may also be a potential biomarker for WT.
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Guochang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
keywords: Axl; Wilms’ tumor; invasion; migration; prognosis; proliferation