Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma.
Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma.
复制标题
靶向人骨肉瘤的后期促进复合物/环体 (APC/C)-含溴结构域 7 (BRD7) 通路
DOI：
10.18632/oncotarget.1816
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发表时间：
2014-05-30
期刊：
影响因子：
--
通讯作者：
Kang T
中科院分区：
文献类型：
--
作者：
Hu K;Liao D;Wu W;Han AJ;Shi HJ;Wang F;Wang X;Zhong L;Duan T;Wu Y;Cao J;Tang J;Sang Y;Wang L;Lv X;Xu S;Zhang RH;Deng WG;Li SP;Zeng YX;Kang T
骨肉瘤是儿童和青少年最常见的原发性恶性骨肿瘤，具有局部浸润和早期肺转移的倾向。然而，目前的治疗方法往往导致化疗耐药，并且临床上没有治疗骨肉瘤的靶点。在这里，我们报告说，BRD 7形成一个复杂的后期促进复合物/环体（APC/C）和APC/Ccdh 1和APC/Ccdc 20在细胞周期中降解。此外，BRD 7是骨肉瘤中的肿瘤抑制因子，并且BRD 7突变体对APC/C降解的抗性在体外和体内抑制骨肉瘤的增殖、集落形成和肿瘤生长方面比野生型蛋白更有效。APC/C抑制剂proTAME与化疗药物的组合在体外有效靶向骨肉瘤。此外，BRD 7与Cdh 1或Cdc 20之间的蛋白水平存在强负相关性，BRD 7表达较低是骨肉瘤患者预后不良的指标。总的来说，我们的研究结果表明，针对APC/C-BRD 7通路可能是治疗骨肉瘤的新策略。
Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence and has a propensity for local invasion and early lung metastasis. However, the current therapies often result in chemoresistance, and a therapeutic target is not available in the clinic for osteosarcoma. Here, we report that BRD7 forms a complex with the anaphase-promoting complex/cyclosome (APC/C) and is degraded by APC/Ccdh1 and APC/Ccdc20 during the cell cycle. Moreover, BRD7 is a tumor suppressor in osteosarcoma, and the BRD7 mutant resistant to degradation by APC/C is more efficient than the wild-type protein at suppressing proliferation, colony formation, and tumor growth of osteosarcoma in vitro and in vivo. The combination of proTAME, an inhibitor of APC/C, with chemotherapeutic drugs efficiently targets osteosarcoma in vitro. Furthermore, there is a strong inverse correlation of protein levels between BRD7 and Cdh1 or Cdc20, and lower BRD7 expression is an indicator for poor prognosis in patients with osteosarcoma. Collectively, our results indicate that targeting the APC/C-BRD7 pathway may be a novel strategy for treating osteosarcoma.
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影响因子：
--
作者：
Lai, Fenju;Hu, Kaishun;Kang, Tiebang
通讯作者：
Kang, Tiebang
DOI：
10.1093/jnci/djs210
发表时间：
2012-05-16
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Tang QL;Xie XB;Wang J;Chen Q;Han AJ;Zou CY;Yin JQ;Liu DW;Liang Y;Zhao ZQ;Yong BC;Zhang RH;Feng QS;Deng WG;Zhu XF;Zhou BP;Zeng YX;Shen JN;Kang T
通讯作者：
Kang T
影响因子：
64.8
作者：
Wei, W;Ayad, NG;Kaelin, WG
通讯作者：
Kaelin, WG
影响因子：
11.2
作者：
Harte, Mary T.;O'Brien, Garrett J.;Harkin, D. Paul
通讯作者：
Harkin, D. Paul
影响因子：
50.3
作者：
Kang, Tiebang;Wei, Yongkun;Piwnica-Worms, Helen
通讯作者：
Piwnica-Worms, Helen