TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ
TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ
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TRIB3通过稳定TAZ赋予食管鳞状细胞癌放疗抵抗力
DOI：
10.1038/s41388-020-1245-0
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发表时间：
2020-03
期刊：
影响因子：
8
通讯作者：
Xi Mian
中科院分区：
文献类型：
--
作者：
Zhou Sha;Liu Shiliang;Lin Chuyong;Li Yue;Ye Liping;Wu Xianqiu;Jian Yunting;Dai Yuhu;Ouyang Ying;Zhao Lei;Liu Mengzhong;Song Libing;Xi Mian
放射抵抗已成为食管鳞癌治疗中减少肿瘤复发、改善预后的主要障碍。因此，迫切需要新的抗辐射ESCC策略。在此，我们报道了tribbles pseudokinase 3（TRIB 3）作为食管鳞癌放射抗性的关键调节因子。TRIB3在ESCC组织和细胞系中过表达。TRIB 3高表达与食管鳞癌患者放疗反应和预后不良显著相关。Trib3在ESCC细胞中的上调通过与TAZ相互作用从而阻碍β-TrCP介导的TAZ泛素化和降解而在体外和体内赋予辐射抗性。相反，沉默TRIB3使ESCC细胞对电离辐射敏感。更重要的是，Trib3与ESCC活检组织中的TAZ活化显著相关，Trib3和TAZ均高表达的患者的放疗反应和生存率最差。我们的研究揭示了ESCC对放射治疗抵抗的关键机制，并为在临床实践中开发基于机制的消除放射抵抗性ESCC的策略提供了新的药理学机会。
Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice.
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影响因子：
3.7
作者：
Sha Zhou;Shiliang Liu;Li Zhang;Suping Guo;Jingxian Shen;Qiaoqiao Li;Hong Yang;Yanfen Feng
通讯作者：
Sha Zhou;Shiliang Liu;Li Zhang;Suping Guo;Jingxian Shen;Qiaoqiao Li;Hong Yang;Yanfen Feng
影响因子：
5.2
作者：
Lee, Yueh-Chun;Wang, Wen-Ling;Chang, Wen-Wei
通讯作者：
Chang, Wen-Wei
影响因子：
9
作者：
Xi, Mian;Yang, Yadi;Lin, Steven H.
通讯作者：
Lin, Steven H.
影响因子：
6.2
作者：
D. Moro;P. Brichon;E. Brambilla;D. Veale;F. Labat;C. Brambilla
通讯作者：
D. Moro;P. Brichon;E. Brambilla;D. Veale;F. Labat;C. Brambilla
TAZ 通过上调人胶质瘤细胞中的 MCL-1 促进替莫唑胺耐药
DOI：
10.1016/j.bbrc.2015.05.115
发表时间：
2015-08-07
影响因子：
3.1
作者：
Tian, Tian;Li, Aimin;Li, Zhaoming
通讯作者：
Li, Zhaoming