The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment.
Carcinogenesis
; 30(3): 377-86, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19136477
ABSTRACT
It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E(2) (PGE(2)) have key roles in influencing the development of colorectal cancer. Deregulation of the COX-2/PGE(2) pathway appears to affect colorectal tumorigenesis via a number of distinct mechanisms promoting tumour maintenance and progression, encouraging metastatic spread, and perhaps even participating in tumour initiation. Here, we review the role of COX-2/PGE(2) signalling in colorectal tumorigenesis and highlight its ability to influence the hallmarks of cancer--attributes defined by Hanahan and Weinberg as being requisite for tumorigenesis. In addition, we consider components of the COX-prostaglandin pathway emerging as important regulators of tumorigenesis; namely, the prostanoid (EP) receptors, 15-hydroxyprostaglandin dehydrogenase and the prostaglandin transporter. Finally, based on recent findings, we propose a model for the cellular adaptation to the hypoxic tumour microenvironment that encompasses the interplay between COX-2, hypoxia-inducible factor 1 and dynamic switches in beta-catenin function that fine-tune signalling networks to meet the ever-changing demands of a tumour.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Dinoprostona
/
Ciclo-Oxigenase 2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Reino Unido