References
Query Results -- Details
MGI Accession ID: MGI:3850564
J Number: J:150340
Other Accession IDs:
Title: Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment.
Authors: Demehri S; Turkoz A; Kopan R
Journal: Cancer Cell
Volume: 16
Issue: 1
Date: 2009 Jul 7
Year: 2009
Pages: 55-66
Review Status: Peer Reviewed
Abstract:
Notch1 is a proto-oncogene in several organs. In the skin, however, Notch1 deletion leads to tumor formation, suggesting that Notch1 is a 'tumor suppressor' within this context. Here we demonstrate that, unlike classical tumor suppressors, Notch1 loss in epidermal keratinocytes promotes tumorigenesis non-cell autonomously by impairing skin-barrier integrity and creating a wound-like microenvironment in the skin. Using mice with a chimeric pattern of Notch1 deletion, we determined that Notch1-expressing keratinocytes in this microenvironment readily formed papillomas, showing that Notch1 was insufficient to suppress this tumor-promoting effect. Accordingly, loss of other Notch paralogues that impaired the skin barrier also predisposed Notch1-expressing skin to tumorigenesis, demonstrating that the tumor-promoting effect of Notch1 loss involves a crosstalk between barrier-defective epidermis and its stroma.
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