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

A Greenhough, HJM Smartt, AE Moore, HR Roberts, AC Williams, C Paraskeva, Abder Kaidi

Research output: Contribution to journalArticle (Academic Journal)peer-review

861 Citations (Scopus)

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 cyclooxygenase-prostaglandin pathway emerging as important regulators of tumorigenesis; namely, the prostanoid (EP) receptors, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and the prostaglandin transporter (PGT). 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 (HIF-1), and dynamic switches in beta-catenin function that fine-tune signalling networks to meet the ever-changing demands of a tumour.
Translated title of the contributionThe COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment
Original languageEnglish
Pages (from-to)377 - 386
Number of pages10
JournalCarcinogenesis
Volume30
Publication statusPublished - Jan 2009

Bibliographical note

Author of Publication Reviewed: Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, Paraskeva C, Kaidi A
Other identifier: PMID: 19136477

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