Sprouty2 suppresses progression and correlates to favourable prognosis of intrahepatic cholangiocarcinoma via antagonizing FGFR 2 signalling

Fibroblast growth factor receptor 2 ( FGFR 2) was demonstrated to correlate to the progression and prognosis of intrahepatic cholangiocarcinoma ( ICC ) by numerous evidences. However, as a well‐recognized suppressor of FGFR 2 signalling, the clinical significance of Sprouty ( SPRY ) family of ICC has not been investigated. In our study, the expressions of SPRY 1‐4 in 20 pairs of fresh tumour tissues were detected with qPCR , and in 108 cases of paraffin‐embedded tissues with immunohistochemistry. The prognostic value of SPRY family in ICC was estimated with univariate analysis and multivariate analysis. As a result, SPRY 2 was identified as an independent prognostic biomarker predicting favourable prognosis of ICC . High SPRY 2 expression was correlated with good differentiation of ICC . With silencing SPRY 2 expression, we demonstrated that SPRY 2 could suppress FGFR 2‐induced ERK phosphorylation, migration, invasion and epithelial‐mesenchymal transition ( EMT ) under FGF 1 stimulation. By overexpressing SPRY 2‐wide type or SPRY 2‐Y55F, the tyrosine‐55 of SPRY 2 was demonstrated to be essential in suppressing ERK phosphorylation, tumour invasion and EMT of ICC cells. In conclusion, SPRY 2 was correlated with favourable prognosis of ICC via suppressing FGFR 2‐induced ERK phosphorylation, invasion and EMT . The phosphorylation of SPRY 2‐Y55 was required in this tumour‐suppressing function of SPRY 2.