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Updated: Jul 22, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression
Klara Balint1, Min Xiao, Chelsea C Pinnix
1The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by beta-catenin, which was upregulated following Notch1 activation. Inhibiting beta-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a beta-catenin-dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma.
Insights
Notch1 signaling promotes primary melanoma growth and metastasis in a stage-specific manner, mediated by beta-catenin. Blocking Notch1 inhibits progression, while activation enhances it in early-stage melanoma.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Notch signaling is crucial for cell fate determination and implicated in various cancers.
- The specific role of Notch signaling in melanoma progression is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of Notch1 signaling in human melanoma development and progression.
Main Methods:
- Analysis of Notch1 pathway activation in human melanoma samples.
- In vitro and in vivo experiments involving Notch signaling inhibition and activation in melanoma cells.
- Assessment of beta-catenin involvement and manipulation.
Main Results:
- Notch1 pathway is activated in human melanoma.
- Notch1 activation enhanced primary melanoma cell growth and metastasis in vitro and in vivo.
- Notch1 had minimal impact on metastatic melanoma cells.
- Beta-catenin upregulation mediated Notch1's oncogenic effects, and its inhibition reversed Notch1-driven progression.
Conclusions:
- Notch1 signaling plays a stage-specific role in promoting primary melanoma progression.
- The observed effects are dependent on beta-catenin.
- Targeting Notch1 and beta-catenin may offer therapeutic strategies for early-stage melanoma.
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