Role of nitric oxide in the regulation of the pro-tumourigenic hypoxic phenotype: From instigation to mitigation

Abstract

Low oxygen levels (hypoxia) are a biophysical consequence of tumour growth that exceeds vascular capacity. Hence, hypoxia is commonly present in solid tumours. Many studies, spanning decades, have demonstrated that the extentof tumour hypoxia is positively correlated with a poor clinical prognosis. These clinical findings have been corroborated with laboratory-based studies demonstrating that hypoxia induces hallmarks of cancer such as metabolic reprogramming, metastatic potential, immune cell evasion and angiogenesis. Accordingly, there has been a great emphasis placed on the need to understand the mechanisms by which hypoxia promotes tumourigenic phenotypes; so that interventional therapeutics can be developed. One candidate modulator of the hypoxic response is Nitric Oxide (NO). In this review, we describe how NO can mimic or mitigate the effects of hypoxia in tumours in a context and concentration-dependent manner. We further reveal emerging research suggesting that NO signalling may be harnessed to prevent tumour progression.