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, Yong Teng

Research output: Contribution to journalArticle

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)13575-13586
Number of pages12
Issue number12
Publication statusPublished - Mar 22 2016
Externally publishedYes



  • E-cadherin
  • EMT
  • FGF19
  • FGFR4
  • GSK3β/β-catenin

ASJC Scopus subject areas

  • Oncology

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