RRC ID 44928
Author Xu YF, Yang XQ, Lu XF, Guo S, Liu Y, Iqbal M, Ning SL, Yang H, Suo N, Chen YX.
Title Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma.
Journal Biochem. Biophys. Res. Commun.
Abstract Fibroblast growth factor receptor 4 (FGFR4) is related to poor prognosis of several cancers, but the correlation between FGFR4 expression and cholangiocarcinoma (CCA) has not been well elucidated. We investigated the expression of FGFR4 in 83 intrahepatic cholangiocarcinomas (IHCCs), 75 perihilar cholangiocarcinomas (PHCCs) and 41 distal cholangiocarcinomas (DCCs) by immunohistochemistry (IHC), and subsequently evaluated association of FGFR4 with clinicopathologic parameters and survival rate. The rate of FGFR4 higher expression was 61.4% (51/83) in IHCCs, 53.3% (40/75) in PHCCs and 56.1% (23/41) in DCCs. FGFR4 expression was significantly related to poor prognosis of IHCC (P=0.002) and PHCC (P=0.019) with univariate analysis, and also identified as an independent prognostic factor in IHCC (P=0.045) and PHCC (P=0.049) with multivariate analysis. Additionally, with functional assays in vitro, we found FGFR4 can induce proliferation, invasion and epithelial-mesenchymal transition (EMT) of CCA cell lines with FGF19 stimulation. Moreover, FGFR4 inhibitor AP24354 can suppress proliferation, invasion and induce apoptosis of CCA cells. In conclusion, FGFR4 expression can be identified as a significant independent prognostic biomarker of IHCC and PHCC. FGFR4 played a pivotal role in proliferation, invasion and EMT of CCA. FGFR4 inhibitor can suppress proliferation, invasion and induce apoptosis of CCA, indicating that FGFR4 may act as a potential therapeutic target.
Volume 446(1)
Pages 54-60
Published 2014-3-28
DOI 10.1016/j.bbrc.2014.02.050
PII S0006-291X(14)00312-X
PMID 24565842
MeSH Aged Apoptosis / drug effects Bile Duct Neoplasms / drug therapy Bile Duct Neoplasms / metabolism* Bile Duct Neoplasms / pathology Bile Ducts, Intrahepatic* Cell Line, Tumor Cell Proliferation / drug effects Cholangiocarcinoma / drug therapy Cholangiocarcinoma / metabolism* Cholangiocarcinoma / pathology Disease Progression Epithelial-Mesenchymal Transition Female Gene Knockdown Techniques HEK293 Cells Hep G2 Cells Humans Imidazoles / pharmacology Liver Neoplasms / drug therapy Liver Neoplasms / metabolism* Liver Neoplasms / pathology Male Middle Aged Neoplasm Invasiveness Prognosis Pyridazines / pharmacology Receptor, Fibroblast Growth Factor, Type 4 / antagonists & inhibitors Receptor, Fibroblast Growth Factor, Type 4 / genetics Receptor, Fibroblast Growth Factor, Type 4 / metabolism* Vascular Endothelial Growth Factor A / metabolism
IF 2.705
Times Cited 22
Human and Animal Cells