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Updated: Aug 6, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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.
Abstract:
Epithelial-to-mesenchymal transition (EMT) plays crucial roles in tumor progression, including cancer cell migration. Non-canonical phosphorylation of the receptor tyrosine kinase EphA2 at Ser-897 via the ERK-RSK pathway also induces cancer cell migration. This non-canonically phosphorylated form of EphA2 has been observed in mesenchymal cells and reported to maintain the functional properties of mesenchymal cells; however, the mechanism of this phosphorylation during EMT remains unclear. We herein demonstrated that level of Ser-897-phosphorylated EphA2 was increased during EMT through the FGFR1-ERK-RSK pathway. EphA2 mRNA expression was also induced, suggesting its modulation by Snail, Slug, and ZEB1. Furthermore, the FGFR1-EphA2 axis promoted cell motility and contributed to poor prognosis in lung adenocarcinoma. Collectively, these results suggest the importance of FGFR1 as a regulator of non-canonical EphA2 activation during EMT.
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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