High expression of Bruton's tyrosine kinase (BTK) is required for EGFR-induced NF-κB activation and predicts poor prognosis in human glioma.
High expression of Bruton's tyrosine kinase (BTK) is required for EGFR-induced NF-κB activation and predicts poor prognosis in human glioma.
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布鲁顿酪氨酸激酶 (BTK) 的高表达是 EGFR 诱导的 NF-κB 激活所必需的，并预测人类神经胶质瘤的不良预后
DOI：
10.1186/s13046-017-0600-7
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发表时间：
2017-09-25
期刊：
影响因子：
--
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Yue C;Niu M;Shan QQ;Zhou T;Tu Y;Xie P;Hua L;Yu R;Liu X
恶性胶质瘤是成人最常见的原发脑肿瘤，预后较差。然而，目前还没有针对胶质瘤患者的有效靶向治疗方法。因此，迫切需要开发新的脑胶质瘤靶向治疗药物。在这项研究中，我们研究了BTK在胶质瘤患者中的表达对预后的意义。此外，我们还研究了伊布鲁替尼在体内外治疗人脑胶质瘤的机制和治疗潜力。我们的数据表明，BTK的高表达是胶质瘤患者预后不良的一个新的预后标志。BTK特异性抑制剂ibrutinib能有效抑制胶质瘤细胞的增殖、迁移和侵袭能力。此外，伊布鲁替尼还可通过调节多种细胞周期相关蛋白诱导细胞周期停滞于G1期。更重要的是，我们发现抑制BTK显著阻断了IκBα的降解，并阻止了EGF诱导的神经胶质瘤细胞中NF-κB p65亚单位的核积聚。综上所述，我们的研究表明BTK是一种新的胶质瘤预后标志物和分子治疗靶点。在表皮生长因子受体诱导的胶质瘤细胞中，BTK是诱导NF-κB活化所必需的。这些发现为未来伊布鲁替尼治疗胶质瘤的临床研究提供了基础。
Malignant glioma is the most common primary brain tumor in adults and has a poor prognosis. However, there are no effective targeted therapies for glioma patients. Thus, the development of novel targeted therapeutics for glioma is urgently needed. In this study, we examined the prognostic significance BTK expression in patients with glioma. Furthermore, we investigated the mechanism and therapeutic potential of ibrutinib in the treatment of human glioma in vitro and in vivo. Our data demonstrate that high expression of BTK is a novel prognostic marker for poor survival in patients with glioma. BTK-specific inhibitor ibrutinib effectively inhibits the proliferation, migration and invasion ability of glioma cells. Furthermore, ibrutinib can induce G1 cell-cycle arrest by regulating multiple cell cycle-associated proteins. More importantly, we found that BTK inhibition significantly blocks the degradation of IκBα and prevents the nuclear accumulation of NF-κB p65 subunit induced by EGF in glioma cells. Taken together, our study suggests that BTK is a novel prognostic marker and molecular therapeutic target for glioma. BTK is required for EGFR-induced NF-κB activation in glioma cells. These findings provide the basis for future clinical studies of ibrutinib for the treatment of glioma.
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影响因子：
7.3
作者：
Pradère JP;Hernandez C;Koppe C;Friedman RA;Luedde T;Schwabe RF
通讯作者：
Schwabe RF
影响因子：
8
作者：
Bonavia, R.;Inda, M. M.;Vandenberg, S.;Cheng, S-Y;Nagane, M.;Hadwiger, P.;Tan, P.;Sah, D. W. Y.;Cavenee, W. K.;Furnari, F. B.
通讯作者：
Furnari, F. B.
影响因子：
28.5
作者：
Mostafa H;Pala A;Högel J;Hlavac M;Dietrich E;Westhoff MA;Nonnenmacher L;Burster T;Georgieff M;Wirtz CR;Schneider EM
通讯作者：
Schneider EM
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW
影响因子：
8
作者：
通讯作者：
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