IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.
Cancer Cell
; 15(2): 103-13, 2009 Feb 03.
Article
em En
| MEDLINE
| ID: mdl-19185845
ABSTRACT
Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Proinflammatory cytokines have been suggested to regulate preneoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-kappaB-regulated cytokine that acts on epithelial and immune cells. Using genetic tools, we now demonstrate that IL-6 is a critical tumor promoter during early CAC tumorigenesis. In addition to enhancing proliferation of tumor-initiating cells, IL-6 produced by lamina propria myeloid cells protects normal and premalignant intestinal epithelial cells (IECs) from apoptosis. The proliferative and survival effects of IL-6 are largely mediated by the transcription factor Stat3, whose IEC-specific ablation has profound impact on CAC tumorigenesis. Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
/
Sobrevivência Celular
/
Interleucina-6
/
Células Epiteliais
/
Fator de Transcrição STAT3
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Mucosa Intestinal
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Neoplasias
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos