Tumor necrosis factor receptor 1/c-Jun-NH2-kinase signaling promotes human neoplasia.
Cancer Res
; 67(8): 3827-34, 2007 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-17440097
ABSTRACT
The tumor necrosis factor alpha receptor (TNFR1) activates downstream effectors that include the mitogen-activated protein kinase kinase 7 (MKK7)/c-Jun-NH(2)-kinase (JNK)/activator protein 1 (AP1) cascade. Here, we report that JNK is activated in a majority of spontaneous human squamous cell carcinomas (SCC). JNK pathway induction bypassed cell cycle restraints induced by oncogenic Ras and cooperated with Ras to convert normal human epidermis into tumors indistinguishable from SCC, confirming its oncogenic potency in human tissue. Inhibiting MKK7, JNK, and AP1 as well as TNFR1 itself using genetic, pharmacologic, or antibody-mediated approaches abolished invasive human epidermal neoplasia in a tumor cell autonomous fashion. The TNFR1/MKK7/JNK/AP1 cascade thus promotes human neoplasia and represents a potential therapeutic target for human epithelial cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Carcinoma de Células Escamosas
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Fator de Transcrição AP-1
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MAP Quinase Quinase 7
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Proteínas Quinases JNK Ativadas por Mitógeno
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Receptores Tipo I de Fatores de Necrose Tumoral
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos