The COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment

Smartt, Helena J.M.; Kaidi, Abderrahmane; Greenhough, Alexander; Moore, Amy E.; Roberts, Heather R.; Williams, Ann C.; Paraskeva, Christos

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. © The Author 2009. Published by Oxford University Press. All rights reserved.

• Journal Article Type: Review
• Acceptance Date: Jan 4, 2009
• Online Publication Date: Jan 9, 2009
• Publication Date: Mar 20, 2009
• Journal: Carcinogenesis
• Print ISSN: 0143-3334
• Electronic ISSN: 1460-2180
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 3
• Pages: 377-386
• DOI: https://doi.org/10.1093/carcin/bgp014
• Keywords: prostaglandins cyclooxygenase-2, signal transduction, cancer, colorectal cancer neoplasms, tumorigenesis, tumour microenvironment, hypoxia
• Public URL: https://uwe-repository.worktribe.com/output/997921
• Publisher URL: https://doi.org/10.1093/carcin/bgp014