神经生长因子IB
生物
黑色素瘤
线粒体
β氧化
细胞生物学
细胞
癌症研究
程序性细胞死亡
核受体
生物化学
脂肪酸
细胞凋亡
转录因子
基因
作者
Xiao-Xue Li,Zhijing Wang,Yu Zheng,Yongjun Guan,Pengbo Yang,Xiang Chen,Cong Peng,Jie He,Yuan-li Ai,Sheng-fu Wu,Kun-Yi Chien,Qiao Wu,Hang-zi Chen
出处
期刊:Molecular Cell
[Elsevier]
日期:2018-02-01
卷期号:69 (3): 480-492.e7
被引量:71
标识
DOI:10.1016/j.molcel.2018.01.001
摘要
Fatty acid oxidation (FAO) is crucial for cells to overcome metabolic stress by providing ATP and NADPH. However, the mechanism by which FAO is regulated in tumors remains elusive. Here we show that Nur77 is required for the metabolic adaptation of melanoma cells by protecting FAO. Glucose deprivation activates ERK2 to phosphorylate and induce Nur77 translocation to the mitochondria, where Nur77 binds to TPβ, a rate-limiting enzyme in FAO. Although TPβ activity is normally inhibited by oxidation under glucose deprivation, the Nur77-TPβ association results in Nur77 self-sacrifice to protect TPβ from oxidation. FAO is therefore able to maintain NADPH and ATP levels and prevent ROS increase and cell death. The Nur77-TPβ interaction further promotes melanoma metastasis by facilitating circulating melanoma cell survival. This study demonstrates a novel regulatory function of Nur77 with linkage of the FAO-NADPH-ROS pathway during metabolic stress, suggesting Nur77 as a potential therapeutic target in melanoma.
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