Expression of GFRα3 correlates with tumor progression and promotes cell metastasis in urothelial carcinoma

BACKGROUND: Urothelial carcinoma (UC) is a major health problem in the general population. We aimed to evaluate the function of GFR alpha 3 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to UC. METHODS: To evaluate the function of GFR alpha 3, a group of 60 pairs of UC patients were recruited in for this study. UC tissues and their adjacent normal control tissues (NCTs) were collected between 2012 and 2015. We used immunohistochemistry to analyze the correlation between GFR alpha 3 expression and clinicopathologic variables and patient survival. The role of regulation of GFR alpha 3 in UC was applied in vitro. In addition, we further investigated the signaling pathway of GFR alpha 3 in UC progression. RESULTS: The expression level of GFR alpha 3 was remarkably upregulated in 49.3% (19/60) patients and downregulated in 25.0% (15/60) patients. The GFR alpha 3 protein expression was upregulated in UC tissues. GFR alpha 3 promotes UC cell migration and invasion in vitro. GFR alpha 3 also promotes UC cell metastasis in vitro. High level of GFR alpha 3 promotes UC cell migration via upregulation of MMP9 expression. CONCLUSIONS: Our results demonstrate that increased GFR alpha 3 expression is significantly correlated with poor prognosis of patients with UC. Thus, GFR alpha 3 might be an important marker and a therapeutic target for UC.