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

Carcinogenesis. 2009 Mar;30(3):377-86. doi: 10.1093/carcin/bgp014. Epub 2009 Jan 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia
  • Cell Movement / physiology
  • Colorectal Neoplasms / blood supply
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / physiology*
  • Dinoprostone / physiology*
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neovascularization, Pathologic / metabolism
  • Organic Anion Transporters / metabolism
  • Receptors, Prostaglandin E / metabolism
  • Signal Transduction / physiology
  • beta Catenin / metabolism


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Organic Anion Transporters
  • Receptors, Prostaglandin E
  • SLCO2A1 protein, human
  • beta Catenin
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Cyclooxygenase 2
  • Dinoprostone