The NOR1/OSCP1 proteins in cancer: from epigenetic silencing to functional characterization of a novel tumor suppressor.

NOR1 (Oxidored-nitro domain-containing protein 1), also known as OSCP1, was first identified in nasopharyngeal carcinoma (NPC) cells in 2003. NOR1 is evolutionarily conserved among species with its expression is restricted to brain, testis and respiratory epithelial cells. NOR1 was downregulated in NPC and the downregulation associates with poor prognosis. Previous study demonstrated that hypermethylation of NOR1 promoter was observed in NPC and hematological malignancies, which has been believed to be the main epigenetic cause for NOR1 silencing in these cancers. Recently, the NOR1 tumor suppressor status has been fully established. NOR1 inhibited cancer cell growth by disturbing tumor cell energe metabolism. NOR1 also promote tumor cells apoptosis in oxidative stress and hypoxia by inhibition of stress induced autophagy. Moreover, NOR1 suppressed cancer cell epithelial-mesenchymal transition, invasion and metastasis via activation of FOXA1/HDAC2-slug regulatory network. Deciphering the molecular mechanisms underlying NOR1 mediated tumor suppressive role would be helpful to a deeper understanding of carcinogenesis and, furthermore, to the development of new therapeutic approaches. Here we summarize the current knowledge on NOR1 focusing on its expression pattern, epigenetic and genetic association with human cancers and its biological functions. This review will also elucidate the potential application of NOR1/OSCP1 for some human malignancies.