FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression

Xiangdong Zhao, Faliang Xu, Nestor P. Dominguez, Yuanping Xiong, Zhongxun Xiong, Hong Peng, Chloe Shay, Yong Teng

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Although genetic amplification and overexpression of the fibroblast growth factor 19 (FGF19) gene are found in human breast cancer, mechanisms that contribute to such functional alterations remain elusive. We report here that high expression of FGF19 is associated with the aggressive malignant behavior and poor survival outcome of breast cancer patients. FGF19 is particularly highly expressed in luminal molecular subtype of breast tumors and its expression levels are positively associated with its secretion levels from breast cancer cells. Genetic knockout of FGF19 significantly induces repression of breast tumor progression and metastasis in either an orthotopic mouse model of breast cancer or an experimental metastasis model. The FGF19 specific receptor, FGFR4, can be activated and subsequently upregulate AKT signaling in breast cancer cell upon FGF19, which is critical for oncogenic role of FGF19. Inactivation of FGFR4 by its inhibitor BLU9931 significantly attenuates FGF19-induced tumor-promoting activity, suggesting interruption of FGFR4 function is sufficient to affect FGF19-driven breast cancer. Overall, these insights support the idea that targeting FGFR4 in breast cancer cells overexpressing FGF19 may represent an effective strategy to suppress cancer development, progression, and metastasis.

Original languageEnglish (US)
Pages (from-to)1616-1625
Number of pages10
JournalMolecular Carcinogenesis
Volume57
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • AKT
  • BLU9931
  • FGF19
  • FGFR4
  • breast cancer
  • invasion and metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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  • Cite this

    Zhao, X., Xu, F., Dominguez, N. P., Xiong, Y., Xiong, Z., Peng, H., Shay, C., & Teng, Y. (2018). FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression. Molecular Carcinogenesis, 57(11), 1616-1625. https://doi.org/10.1002/mc.22884