Melanoma gets a new NOTCH in its belt, and a new treatment strategy

Main Category: Melanoma / Skin Cancer
Article Date: 24 Oct 2005 - 0:00 PDT

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Notch is a cellular receptor that is necessary for proper tissue development and maintenance. The Notch signaling pathway is involved in several cancers, but its role in melanoma was poorly characterized. In a paper appearing online on October 20 in advance of print publication of the November issue of the Journal of Clinical Investigation, Meenhard Herlyn and colleagues from the Wistar Institute describe a specific role of Notch1 signaling in primary melanoma progression.

The authors show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed, while constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth but had little effect on metastatic melanoma cells. Activation of Notch1 signaling enables primary melanoma cells to gain metastatic capability.

Notch effects on primary melanoma cells is mediated through beta-catenin. These findings not only define a novel role for Notch1 signaling in promoting primary melanoma progression but also unveil a beta-catenin-dependent mechanism for the stage- specific role of Notch1 signaling in melanoma progression. Therefore, members of the Notch pathway and beta-catenin pathway are potential targets for therapy in melanoma and skin cancers.

TITLE: Activation of Notch1 signaling is required for beta-catenin-mediated human primary melanoma progression

View the PDF of this article at: the-jci.org/article.php?id=25001

Stacie Bloom
press_releases@the-jci.org
212-342-4159
Journal of Clinical Investigation
jci.org

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