IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes.
EMBO J
; 30(22): 4571-85, 2011 Nov 16.
Article
en En
| MEDLINE
| ID: mdl-21909072
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Queratinocitos
/
Factores Reguladores del Interferón
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Receptor Notch1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suiza