Is 15-LOX-1 a tumor suppressor?

A number of enzymes in the cyclooxygenase and lipoxygenase pathways process fatty acids to generate a variety of bioactive lipids. Recent findings that link inflammation to carcinogenesis have started to reveal how these bioactive lipids function in cellular signaling pathways as lipid messengers that mediate responses to cellular injury through inflammatory processes (1). Downstream effects of these bioactive lipids are determined by tissue-specific isomerases and specific receptors present in different organs. Two main pathways lead to the generation of bioactive lipids, which differ markedly in their biological activities. The cyclooxygenases lead mostly to the generation of prostaglandins and thromboxanes, whereas the lipoxygenases lead to the formation of leukotrienes and lipoxins among other products (Figure 1). Collectively, these signaling 20-carbon fatty acids are termed eicosanoids. They act by autocrine and paracrine mechanisms to regulate the dynamics of inflammation, immunity, and smooth muscle contraction and as messengers in the central nervous system (1,2). It is not surprising that many of these bioactive molecules play a critical role in inflammation, but their opposing functions are often underappreciated. The role of inflammation in carcinogenesis is well established and has been summarized by Wang and Dubois (1); however, important questions remain. It is still not clear which specific component(s) or which phase(s) of the inflammatory process are involved in carcinogenesis or at which stage of carcinogenesis the primary effects of inflammation occur. Furthermore, the key question of whether inflammation alone is sufficient and necessary to promote carcinogenesis in Is 15-LOX-1 a Tumor Suppressor?