Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect.
Glycolysis maintains AMPK activation in sorafenib-induced Warburg effect.
复制标题
DOI：
10.1016/j.molmet.2023.101796
复制
发表时间：
2023-11
影响因子：
8.1
通讯作者：
Wang, Huan
中科院分区：
文献类型：
--
作者：
Guo, Sijia;Zhang, Chenhao;Zeng, Haiou;Xia, Yantao;Weng, Chenghao;Deng, Yichen;Wang, Luda;Wang, Huan
肝细胞癌（HCC）是世界上第二大致命癌症，目前仍缺乏治愈性治疗。有氧糖酵解或Warburg效应是一线HCC治疗索拉非尼诱导的主要耐药机制，由代谢的主要调节因子AMPK调节。AMPK的活化是产生抗性所必需的；然而，AMPK的活化动力学及其调控研究却很少。工程细胞表达AMPK活性生物传感器，我们在索拉非尼诱导的耐药过程中以高通量方式监测单个HCC细胞中AMPK的激活。索拉非尼诱导AMPK的短暂激活，其持续时间取决于葡萄糖。抑制糖酵解可缩短AMPK的活化；而增加糖酵解会增加其激活持续时间。我们的数据强调AMPK的激活持续时间对癌症逃避治疗很重要，糖酵解是AMPK激活持续时间的关键调节因子。在索拉非尼诱导的耐药过程中，AMPK活性在单个癌细胞中以高通量方式进行监测。索拉非尼诱导AMPK的短暂激活，其持续时间取决于葡萄糖。抑制糖酵解会缩短AMPK的激活时间，而增加糖酵解会延长其激活时间。AMPK的长期激活对于逃避索拉非尼诱导的肝细胞癌细胞杀伤是重要的。
Hepatocellular carcinoma (HCC) is the second deadly cancer in the world and still lacks curative treatment. Aerobic glycolysis, or Warburg effect, is a major resistance mechanism induced by first-line treatment of HCC, sorafenib, and is regulated by the master regulator of metabolism, AMPK. Activation of AMPK is required for resistance; however, activation dynamics of AMPK and its regulation is rarely studied. Engineering cells to express an AMPK activity biosensor, we monitor AMPK activation in single HCC cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation; whereas increasing glycolysis increases its activation duration. Our data highlight that activation duration of AMPK is important for cancer evasion of therapeutic treatment and glycolysis is a key regulator of activation duration of AMPK. AMPK activity is monitored in single cancer cells in a high throughput manner during sorafenib-induced drug resistance. Sorafenib induces transient activation of AMPK, duration of which is dependent on glucose. Inhibiting glycolysis shortens AMPK activation, whereas increasing glycolysis increases its activation duration. Prolonged activation of AMPK is important for evasion of sorafenib-induced cell killing in hepatocellular carcinoma.
登录
查看更多内容
影响因子：
8.8
作者：
Miyamoto T;Rho E;Sample V;Akano H;Magari M;Ueno T;Gorshkov K;Chen M;Tokumitsu H;Zhang J;Inoue T
通讯作者：
Inoue T
影响因子：
7.7
作者：
Hardie DG
通讯作者：
Hardie DG
低剂量索拉非尼作为线粒体解偶联剂并改善非酒精性脂肪性肝炎
影响因子：
29
作者：
Jian, Chongshu;Fu, Jiajun;Cheng, Xu;Shen, Li-Jun;Ji, Yan-Xiao;Wang, Xiaoming;Pan, Shan;Tian, Han;Tian, Song;Liao, Rufang;Song, Kehan;Wang, Hai-Ping;Zhang, Xin;Wang, Yibin;Huang, Zan;She, Zhi-Gang;Zhang, Xiao-Jing;Zhu, Lihua;Li, Hongliang
通讯作者：
Li, Hongliang
阿司匹林通过抑制 PFKFB3 克服肝细胞癌中的索拉非尼耐药
影响因子：
6.4
作者：
Li, Sainan;Dai, Weiqi;Guo, Chuanyong
通讯作者：
Guo, Chuanyong
影响因子：
13.6
作者：
Hung CM;Lombardo PS;Malik N;Brun SN;Hellberg K;Van Nostrand JL;Garcia D;Baumgart J;Diffenderfer K;Asara JM;Shaw RJ
通讯作者：
Shaw RJ