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.
Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China, xiangbolin@csu.edu.cn.
Bo
B
Xiang
Mei
M
Yi
Wenjuan
W
Li
Wei
W
Wang
Pan
P
Zheng
Xiaoling
X
Li
Guiyuan
G
Li
D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma; D015687:Cell Hypoxia / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D010101:Oxygen Consumption / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051028:bcl-2-Associated X Protein / Q000235:genetics
D026901:Membrane Transport Proteins; C479458:OSCP1 protein, human; C000631429:PDK1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases