A Role for Nitric Oxide and for Nitric Oxide Synthases in Tumor Biology

The dual role of nitric oxide in cancer biology is discussed here through the perspective of our work on nitric oxide-mediated signaling events. The nitric oxide-stimulated Src-FAK and Ras-ERK1/2 mitogen-activated protein kinases (MAPKs) oncogenic signaling pathways are discussed, highlighting the cross-talk between 2 major posttrans- lational modifications: protein phosphorylation and protein S-nitrosylation. In addition, we discuss the importance of nitric oxide synthases in cancer biology, focusing on the roles of endothelial nitric oxide synthase and arginase 2 in human thyroid tumor progression. A direct relationship between the expression levels of both enzymes was found in human follicular thyroid carcinoma. Finally, the antioncogenic, proapoptotic actions of nitric oxide based on its anti- adhesive properties are presented and discussed.