Nitric Oxide and Aggressive Behavior of Lung Cancer Cells

Abstract

Nitric oxide (NO) is an important cell signaling molecule whose level is frequently elevated in many tumors including that of lung. Cellular phenotypes and behaviors are influenced by NO found in proximity to the tumor, namely the tumor microenvironment. In lung cancer, a high level of NO is linked to advanced stage and poor survival of patients. This review describes the promotory role of NO in aggressive behavior of lung cancer cells with a focus on apoptosis and anoikis resistance, cell migration and invasion and cancer stem cells, all of which are key determinants of cancer relapse and metastasis. We specifically address the effects of NO on the modulations of structure, stability, function and activity of key proteins, and discuss how these changes could affect aggressive behavior. Such knowledge will encourage additional experimental and clinical investigations that contribute to the understanding of the molecular basis of cancer pathophysiology which could lead to targeted cancer therapy.

Keywords: Nitric oxide; apoptosis; cancer stem cells; lung cancer; metastasis; migration; review.