| First Author | Demehri S | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 1 | Pages | 55-66 |
| PubMed ID | 19573812 | Mgi Jnum | J:150340 |
| Mgi Id | MGI:3850564 | Doi | 10.1016/j.ccr.2009.05.016 |
| Citation | Demehri S, et al. (2009) Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell 16(1):55-66 |
| abstractText | 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. |
