| First Author | Restivo G | Year | 2011 |
| Journal | EMBO J | Volume | 30 |
| Issue | 22 | Pages | 4571-85 |
| PubMed ID | 21909072 | Mgi Jnum | J:180027 |
| Mgi Id | MGI:5305005 | Doi | 10.1038/emboj.2011.325 |
| Citation | Restivo G, et al. (2011) IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. EMBO J 30(22):4571-85 |
| abstractText | While the pro-differentiation and tumour suppressive functions of Notch signalling in keratinocytes are well established, the underlying mechanisms remain poorly understood. We report here that interferon regulatory factor 6 (IRF6), an IRF family member with an essential role in epidermal development, is induced in differentiation through a Notch-dependent mechanism and is a primary Notch target in keratinocytes and keratinocyte-derived SCC cells. Increased IRF6 expression contributes to the impact of Notch activation on growth/differentiation-related genes, while it is not required for induction of 'canonical' Notch targets like p21(WAF1/Cip1), Hes1 and Hey1. Down-modulation of IRF6 counteracts differentiation of primary human keratinocytes in vitro and in vivo, promoting ras-induced tumour formation. The clinical relevance of these findings is illustrated by the strikingly opposite pattern of expression of Notch1 and IRF6 versus epidermal growth factor receptor in a cohort of clinical SCCs, as a function of their grade of differentiation. Thus, IRF6 is a primary Notch target in keratinocytes, which contributes to the role of this pathway in differentiation and tumour suppression. |
