To summarize, our results identified decreased eNOS activity and phosphorylation resulting in an NO-deficiency state as an early event in breast cancer pulmonary metastasis, that occurs prior to the decrease in expression of endothelium-specific markers that indicates functional phenotypic switch of pulmonary endothelium toward a mesenchymal phenotype (EndMT), coinciding with development of the first metastatic nodules in the lungs and metastatic tissue remodeling. The gene discussed is NOS3; the disease is breast cancer.