...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >Class III β-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer
【24h】

Class III β-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer

机译：第三类β微管蛋白和细胞骨架的网关卵巢癌耐药

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Class III β-tubulin isotype (βIII-tubulin) is a predictive biomarker in ovarian cancer and other solid tumor malignancies. We discovered that βIII-tubulin function is linked to two GTPases: guanylate-binding protein 1 (GBP1), which activates its function, and GNAI1, which inhibits it. This finding was demonstrated in a panel of ovarian cancer cells resistant to several chemotherapeutic agents. Using a protein microarray, we identified PIM1 as the downstream partner of GBP1, recruited into the cytoskeleton under hypoxic conditions. The clinical value of these observations was tested by performing an archive study of 98 ovarian cancer patients, which demonstrated that the βIII-tubulin -/PIM1- cohort responded to treatment, exhibiting long overall survival (OS), while βIII-tubulin +/PIM+ patients experienced poor outcomes and OS times similar to patients receiving palliation alone. βIII-tubulin expression is commonly believed responsible for paclitaxel resistance due to its enhancement of the dynamic instability of microtubules, which counteracts the activity of taxanes. In contrast, our research reveals that βIII-tubulin behaves as a gateway for prosurvival signals, such as PIM1, to move into the cytoskeleton. When cells are exposed to microenvironmental stressors, they activate this pathway by telling the cytoskeleton to incorporate PIM1 through GBP1 and βIII-tubulin, which ultimately leads to drug resistance. This discovery reveals that βIII-tubulin does not act alone but requires partners to play its role. The discovery of such protein:protein interactions underlying this prosurvival cascade makes feasible the development of therapeutic approaches using novel compounds that are capable of inhibiting the transmission of prosurvival signals into the cytoskeleton.
机译：第三类β微管蛋白同形像(βIII-tubulin)卵巢癌和预测生物标志物其他实体瘤恶性肿瘤。,βIII-tubulin函数与两个gtpase: guanylate-binding蛋白1(1英镑),激活其功能,GNAI1,抑制它。卵巢癌细胞耐药许多化疗药物。微阵列,我们认为PIM1下游1英镑伙伴,加入了细胞骨架在缺氧条件下。这些观察是通过执行一个测试档案98名卵巢癌患者的研究中,这表明,βIII-tubulin - / PIM1吗群体对治疗,表现出长总生存期(OS),而βIII-tubulin + / PIM +病人经历了糟糕的结果和操作系统类似于患者缓解孤独。通常认为βIII-tubulin表达式由于其负责紫杉醇阻力增强的动态不稳定微管,抵消的活动紫杉烷。βIII-tubulin行为作为prosurvival网关信号,如PIM1,进入细胞骨架。微环境的压力,他们激活通路,告诉细胞骨架合并PIM1通过英镑1和βIII-tubulin,最终导致耐药性。发现表明,βIII-tubulin不采取行动但是需要伙伴发挥作用。发现这种蛋白质:蛋白质相互作用底层这prosurvival级联可行的治疗的发展方法使用新颖的化合物,有能力抑制prosurvival的传播信号到细胞骨架。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号