Many actions of cyclooxygenase‐2 in cellular dynamics and in cancer

<jats:title>Abstract</jats:title><jats:p>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. J. Cell. Physiol. 190: 279–286, 2002. © 2002 Wiley‐Liss, Inc.</jats:p>