Research Papers:

FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation

Huakan Zhao, Fenglin Lv, Guizhao Liang, Xiaobin Huang, Gang Wu, Wenfa Zhang, Le Yu, Lei Shi and Yong Teng _

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Oncotarget. 2016; 7:13575-13586. https://doi.org/10.18632/oncotarget.6185

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Huakan Zhao1, Fenglin Lv1, Guizhao Liang1, Xiaobin Huang1, Gang Wu2, Wenfa Zhang1, Le Yu1, Lei Shi1, Yong Teng1

1School of Life Sciences and School of Bioengineering, Chongqing University, Chongqing, PR China

2Third Affiliated Hospital, Third Military Medical University, Chongqing, PR China

Correspondence to:

Yong Teng, e-mail: [email protected]

Keywords: FGF19, FGFR4, EMT, E-cadherin, GSK3β/β-catenin

Received: May 25, 2015     Accepted: October 04, 2015     Published: October 20, 2015


Compelling evidence suggests that the epithelial-mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. FGF19 has been shown to be involved in EMT in cholangiocarcinoma and colorectal cancer, however, molecular mechanisms underlying FGF19-induced EMT process in hepatocellular carcinoma (HCC) remain largely unknown. Here, we show the expression of FGF19 is significantly elevated and negatively associated with the expression of E-cadherin in HCC tissues and cell lines. Ectopic FGF19 expression promotes EMT and invasion in epithelial-like HCC cells through repression of E-cadherin expression, whereas FGF19 knockdown enhances E-cadherin expression and hence diminishes EMT traits in mesenchymal-like HCC cells, suggesting FGF19 exerts its tumor progressing functions as an EMT inducer. Interestingly, depletion of FGF19 cannot abrogate EMT traits in the presence of GSK3β inhibitors. Furthermore, FGF19-induced EMT can be markedly attenuated when FGFR4 is knocked out. These observations clearly indicate that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC.

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