Many actions of cyclooxygenase-2 in cellular dynamics and in cancer.
Cyclooxygenase-2 (COX-2) is the inducible isoform of cyclooxygenase, the enzyme that catalyzes the rate-limiting step in prostaglandin synthesis from arachidonic acid. Various prostaglandins are produced in a cell type-specific manner, and they elicit cellular functions via signaling through G-protein coupled membrane receptors, and in some cases, through the nuclear receptor PPAR. COX-2 utilization of arachidonic acid also perturbs the level of intracellular free arachidonic acid and subsequently affects cellular functions. In a number of cell and animal models, induction of COX-2 has been shown to promote cell growth, inhibit apoptosis and enhance cell motility and adhesion. The mechanisms behind these multiple actions of COX-2 are largely unknown. Compelling evidence from genetic and clinical studies indicates that COX-2 upregulation is a key step in carcinogenesis. Overexpression of COX-2 is sufficient to cause tumorigenesis in animal models and inhibition of the COX-2 pathway results in reduction in tumor incidence and progression. Therefore, the potential for application of non-steroidal anti-inflammatory drugs as well as the recently developed COX-2 specific inhibitors in cancer clinical practice has drawn tremendous attention in the past few years. Inhibition of COX-2 promises to be an effective approach in the prevention and treatment of cancer, especially colorectal cancer.
Cao
Yang
Y
Huntsman Cancer Institute, University of Utah, Salt Lake City 84112, USA.
Prescott
Stephen M
SM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002468:Cell Physiological Phenomena; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases