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GPNMB is a novel binding partner of FGFR1 that affects tumorigenic potential through AKT phosphorylation in TNBC

  • 0Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.
Cancer Science +

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November 28, 2024

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November 28, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Glycoprotein nonmetastatic melanoma protein B (GPNMB) and fibroblast growth factor receptor 1 (FGFR1) are key drivers in aggressive triple-negative breast cancer (TNBC). Their interaction promotes tumor growth and reduces survival, offering potential therapeutic targets.

Area Of Science

  • Oncology
  • Molecular Biology
  • Biochemistry

Background

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
  • Glycoprotein nonmetastatic melanoma protein B (GPNMB) is overexpressed in TNBC and linked to poor prognosis.
  • Fibroblast growth factor receptor 1 (FGFR1) signaling is enhanced in invasive breast cancer.

Purpose Of The Study

  • To investigate the role of GPNMB and FGFR1 in TNBC progression.
  • To elucidate the molecular interaction between GPNMB and FGFR1.
  • To identify potential therapeutic targets for TNBC.

Main Methods

  • Bioinformatic analyses of patient data.
  • In silico protein-protein docking and molecular dynamics simulations.
  • In vitro studies using TNBC cell lines to assess GPNMB and FGFR1 interaction and functional impact.

Main Results

  • GPNMB and FGFR1 co-expression is associated with lower relapse-free survival in breast cancer patients.
  • GPNMB and FGFR1 are crucial for TNBC cell sphere formation, migration, and epithelial-mesenchymal transition (EMT).
  • GPNMB isoform b binds with high affinity to FGFR1 isoform c (FGFR1c), correlating with cancer aggressiveness.
  • GPNMB facilitates AKT phosphorylation, enhancing FGFR1c binding and TNBC cell tumorigenicity.

Conclusions

  • GPNMB and FGFR1 form a critical complex that drives TNBC aggressiveness.
  • Targeting the GPNMB-FGFR1 interaction and downstream AKT signaling may offer a novel therapeutic strategy for TNBC.

Keywords:

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