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- Title
The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment.
- Authors
Alexander Greenhough; Helena J.M. Smartt; Amy E. Moore; Heather R. Roberts; Ann C. Williams; Christos Paraskeva; Abderrahmane Kaidi
- Abstract
It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E2 (PGE2) have key roles in influencing the development of colorectal cancer. Deregulation of the COX-2/PGE2 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/PGE2 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 β-catenin function that fine-tune signalling networks to meet the ever-changing demands of a tumour.
- Subjects
CYCLOOXYGENASE 2; CARCINOGENESIS; COLON cancer; PROSTAGLANDINS E; CANCER cell adaptation; MICROBIOLOGY; CELLULAR signal transduction
- Publication
Carcinogenesis, 2009, Vol 30, Issue 3, p377
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgp014