NOS2 as an Emergent Player in Progression of Cancer

Although the inducible form of nitric oxide synthase (NOS2) was initially shown to be a major player as an antitumor component of the immune response, more recent data have shown that NOS2 expression in cancer cells often predicts poor outcome. Unlike growth factors associated with a single oncogenic pathway, nitric oxide (NO) has a ubiquitous nature wherein it simultaneously mediates major oncogenic pathways from Akt/PI3K and RAS/ERK to HIF1a and TGFb. These interactive loops perpetuate oncogenic mechanism that leads to increased cancer stemness, proliferation metastasis, chemoresistance, angiogenesis, and immunosuppression. Examination of a wide variety of patient tumors demonstrates that NOS2 expression is >50% for most cancers. In many cases, elevated NOS2 has been shown to predict poor outcome in cancer such as ER- breast cancer, glioma, melanoma, cervical, liver, ovarian, and pancreatic. Taken together, NOS2 may be one of the most powerful biomarker and predictors of poor prognosis and an ideal target for cancer therapy. Antioxid. Redox Signal. 26, 963-965.