Related Experiment Video
Updated: Jun 7, 2026
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Notch signaling activation suppresses v-Src-induced transformation of neural cells by restoring TGF-β-mediated
Samira Amarir1, Maria Marx, Georges Calothy
1CNRS UMR3347/INSERM U1021, Institut Curie-Section Recherche, Orsay, France.
Background:
We have been investigating how interruption of differentiation contributes to the oncogenic process and the possibility to reverse the transformed phenotype by restoring differentiation. In a previous report, we correlated the capacity of intracellular Notch (ICN) to suppress v-Src-mediated transformation of quail neuroretina (QNR/v-src(ts)) cells with the acquisition by these undifferentiated cells of glial differentiation markers.
Methodology/Principal Findings:
In this work, we have identified autocrine TGF-β3 signaling activation as a major effector of Notch-induced phenotypic changes, sufficient to induce transition in differentiation markers expression, suppress morphological transformation and significantly inhibit anchorage-independent growth. We also show that this signaling is constitutive of and contributes to ex-vivo autonomous QNR cell differentiation and that its down-regulation is essential to achieve v-Src-induced transformation.
Conclusions/Significance:
These results support the possibility that Notch signaling induces differentiation and suppresses transformation by a novel mechanism, involving secreted proteins. They also underline the importance of extracellular signals in controlling the balance between normal and transformed phenotypes.
Insights
Notch signaling suppresses cancer development by activating TGF-β3, promoting cell differentiation and inhibiting tumor growth. Restoring differentiation offers a potential strategy to reverse the transformed cell phenotype.
Area of Science:
- Cell biology
- Cancer research
- Molecular signaling
Background:
- Investigating the role of differentiation interruption in oncogenesis.
- Exploring the potential to reverse cancer phenotypes by restoring differentiation.
- Previous work linked intracellular Notch (ICN) to glial differentiation marker acquisition in quail neuroretina (QNR/v-src(ts)) cells, suppressing v-Src-mediated transformation.
Purpose of the Study:
- To identify the molecular mechanisms by which Notch signaling suppresses cellular transformation.
- To elucidate the role of autocrine signaling in Notch-induced differentiation and phenotypic changes.
- To understand the interplay between extracellular signals and the balance between normal and transformed cell phenotypes.
Main Methods:
- Analysis of Notch-induced phenotypic changes in QNR/v-src(ts)) cells.
- Identification of key signaling pathways involved in Notch-mediated effects.
- Assessment of differentiation markers, cell morphology, and anchorage-independent growth.
Main Results:
- Autocrine transforming growth factor-beta 3 (TGF-β3) signaling activation identified as a key effector of Notch-induced changes.
- Notch-induced TGF-β3 signaling suppresses morphological transformation and inhibits anchorage-independent growth.
- TGF-β3 signaling is crucial for QNR cell differentiation and its downregulation is necessary for v-Src-induced transformation.
Conclusions:
- Notch signaling suppresses cellular transformation and induces differentiation via a novel mechanism involving secreted proteins, specifically TGF-β3.
- Autocrine TGF-β3 signaling plays a critical role in mediating Notch's anti-transforming effects.
- Extracellular signals are crucial regulators of the balance between normal and cancerous cell phenotypes, highlighting potential therapeutic targets.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:16TGF - β Signaling Pathway
02:33Hedgehog Signaling Pathway
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...