FGFR1 induces RSK-dependent non-canonical activation of EphA2 during EMT

Yue Zhou1, Leixin Song2, Tomohiro Yamamura1

  • 1Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.

Insights

Fibroblast growth factor receptor 1 (FGFR1) activates non-canonical EphA2 phosphorylation during epithelial-mesenchymal transition (EMT), promoting cancer cell migration and poor prognosis in lung adenocarcinoma.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Epithelial-to-mesenchymal transition (EMT) is critical for tumor progression and cancer cell migration.
  • Non-canonical phosphorylation of EphA2 (Ephrin A2 receptor) at Ser-897 by the ERK-RSK pathway promotes cancer cell migration.
  • The mechanism linking EMT and non-canonical EphA2 phosphorylation remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of non-canonical EphA2 phosphorylation during EMT.
  • To investigate the role of FGFR1 in regulating EphA2 phosphorylation and cancer cell migration during EMT.

Main Methods:

  • Western blotting to detect phosphorylated EphA2.
  • Quantitative PCR to analyze EphA2 mRNA expression.
  • Analysis of FGFR1-EphA2 signaling axis in lung adenocarcinoma samples.

Main Results:

  • Ser-897 phosphorylated EphA2 levels increased during EMT via the FGFR1-ERK-RSK pathway.
  • EMT induced EphA2 mRNA expression, potentially modulated by Snail, Slug, and ZEB1.
  • The FGFR1-EphA2 axis was found to promote cell motility and correlate with poor prognosis in lung adenocarcinoma.

Conclusions:

  • FGFR1 is a key regulator of non-canonical EphA2 activation during EMT.
  • The FGFR1-EphA2 signaling pathway contributes to cancer cell migration and poor prognosis in lung adenocarcinoma.

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