Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression.

Hypoxia is a characteristic pathophysiological property of locally advanced solid tumors and a relevant factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Tumors alter their metabolic pathways to survive in nutrient and oxygen poor microenvironments by a process known as the "Warburg Effect." The current studies identify a novel tumor suppressor gene, termed oxidored nitro domain-containing protein 1 (NOR1) which alters hypoxia cellular response in nasopharyngeal carcinoma. NOR1 expression causes apoptosis of tumor cells in hypoxia by altering the expression of PDK1 expression and mitochondrial Bax-Bcl2 balance thus suppress tumor cell adaptation to hypoxia. Although the importance of hypoxia cellular response is well documented in tumor progression, this is the first demonstration of a human tumor suppressor which functions by regulating mitochondrial apoptotic pathways to suppress tumor survival in oxygen poor microenvironments.