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Updated: Jul 24, 2026
08:01
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Notch activation suppresses fibroblast growth factor-dependent cellular transformation
Deena Small1, Dmitry Kovalenko, Raffaella Soldi
1Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
The Journal of Biological Chemistry
|February 25, 2003
Summary
Suppressing Notch signaling in NIH 3T3 cells promotes fibroblast growth factor receptor (FGFR)-dependent transformation. This involves increased FGF release and signaling, revealing a reciprocal regulatory mechanism between Notch and FGFR pathways in cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Aberrant activation of Notch and fibroblast growth factor receptor (FGFR) signaling pathways is linked to neoplastic growth.
- Understanding the interplay between these pathways is crucial for comprehending cell growth regulation and cancer development.
Purpose of the Study:
- To investigate the functional relationship between Notch and FGFR signaling pathways.
- To determine how suppression of Notch signaling affects FGFR-dependent cellular phenotypes.
Main Methods:
- Utilized NIH 3T3 cells with suppressed Notch signaling via Jagged1 or dominant-negative Notch forms.
- Assessed anchorage-independent growth in soft agar.
- Analyzed FGF gene expression and FGF1 export.
- Investigated the effect of FGF on CSL-dependent transcription.
- Examined the impact of constitutively active Notch forms on FGF release and FGFR signaling.
Main Results:
- Notch suppression led to an exaggerated FGF-dependent transformed phenotype, including anchorage-independent growth.
- This phenotype was associated with increased FGF gene expression and FGF1 extracellular export.
- FGF signaling negatively regulated Notch by suppressing CSL-dependent transcription.
- Active Notch forms counteracted FGF1 release and FGFR-mediated effects.
Conclusions:
- A reciprocal autoregulatory mechanism exists between Notch and FGFR signaling pathways.
- This communication is important for the regulation of normal cell growth.
- Dysregulation of this interplay may contribute to neoplastic processes.
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