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FGF10/FGFR2 Signaling: Therapeutically Targetable Vulnerability in Ligand-responsive Cholangiocarcinoma Cells

Kimyeun Oeurn1,2, Apinya Jusakul2,3, Rattanaporn Jaidee1,2

  • 1Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

In Vivo (Athens, Greece)
|June 27, 2023
PubMed
Abstract

Insights

Fibroblast growth factor 10 (FGF10) activates Fibroblast growth factor receptor 2 (FGFR2) signaling, promoting cholangiocarcinoma (CCA) cell migration. FGFR inhibitors suppress this FGF10-mediated migration, suggesting potential therapeutic applications for CCA.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Fibroblast growth factor receptor 2 (FGFR2) is a validated therapeutic target in cholangiocarcinoma (CCA).
  • The role of FGF10 ligand in activating FGFR2 and its downstream oncogenic pathways in CCA remains to be fully elucidated.

Purpose of the Study:

  • To investigate the mechanisms by which FGF10 activates FGFR2 in CCA cells.
  • To determine if FGFR inhibitors can suppress FGF10-mediated CCA cell migration.

Main Methods:

  • Assessed FGF10 effects on proliferation, migration, and invasion using clonogenic and transwell assays.
  • Quantified protein expression of FGFR2 and pro-angiogenic factors via immunoblotting and antibody arrays.
  • Utilized FGFR2 knockdown and an FGFR inhibitor (infigratinib) to evaluate pathway activation and therapeutic efficacy.

Main Results:

  • FGF10 significantly increased proliferation, migration, and invasion, alongside phospho-FGFR/FGFR2 expression in KKU-M213A cells.
  • FGF10 upregulated key pro-metastatic proteins including p-Akt, p-mTOR, VEGF, and Slug.
  • FGFR2 knockdown and FGFR inhibitor treatment markedly suppressed FGF10-mediated cell migration.

Conclusions:

  • FGF10/FGFR2 signaling activates Akt/mTOR and VEGF/Slug pathways, driving CCA cell migration and invasion.
  • FGFR inhibitors effectively suppress FGF10/FGFR2-driven cell migration, indicating potential clinical utility in CCA treatment.
Keywords:
FGF10FGFR2cholangiocarcinomainfigratinibmetastasis

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