Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression
Expression of oxidored nitro domain-containing protein 1(NOR1) impairs nasopharyngeal carcinoma cells adaptation to hypoxia and inhibits PDK1 expression
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DOI：
10.1007/s11010-014-2072-9
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发表时间：
2014-05
影响因子：
4.3
通讯作者：
Bo Xiang;Mei Yi;Wen-juan Li;Wei Wang;Pan Zheng;Xiaoling Li;Gui-yuan Li
中科院分区：
文献类型：
--
作者：
Bo Xiang;Mei Yi;Wen-juan Li;Wei Wang;Pan Zheng;Xiaoling Li;Gui-yuan Li
缺氧是局部晚期实体瘤的特征性病理生理学特性，也是肿瘤（病理）生理组的相关因素，因为它可以促进肿瘤进展和对治疗的抵抗。肿瘤通过称为“瓦尔堡效应”的过程改变其代谢途径，以在营养和氧气匮乏的微环境中生存。目前的研究发现了一种新型肿瘤抑制基因，称为氧化硝基结构域蛋白 1 (NOR1)，它可以改变鼻咽癌的缺氧细胞反应。 NOR1的表达通过改变PDK1的表达和线粒体Bax-Bcl2的平衡而导致肿瘤细胞在缺氧时凋亡，从而抑制肿瘤细胞对缺氧的适应。尽管缺氧细胞反应在肿瘤进展中的重要性已得到充分证明，但这是人类肿瘤抑制因子的首次证明，其通过调节线粒体凋亡途径发挥作用，以抑制缺氧微环境中的肿瘤存活。
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.