一个具有潜在临床实用性的结肠癌子组的脆弱性
Loredana Vecchione1, Valentina Gambino1, Jonne Raaijmakers2
1Division of Molecular Carcinogenesis and Cancer Genomics Center Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Cell
|April 9, 2016
概括
研究人员确定RAN结合蛋白2 (RANBP2) 对类似BRAF的结肠癌生存至关重要. 抑制RANBP2导致细胞死亡,这些瘤对潜在的向治疗方法维诺雷尔宾的敏感性增加.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- BRAF (V600E) 突变性结肠癌与一些非突变性瘤具有共同的基因表达特征,称为"BRAF-like"瘤.
- 类似BRAF的瘤约占所有结肠癌的20%.
- 识别BRAF类CC的特定漏洞对于开发向疗法至关重要.
研究的目的:
- 通过基因查来确定类似BRAF的结肠癌亚型的治疗弱点.
- 调查RANBP2 (NUP358) 在BRAF类CC细胞存活中的作用.
- 探索维诺尔宾作为针对BRAF类CC的向治疗的潜力.
主要方法:
- 使用基于shRNA的基因选,针对BRAF (V600E) 基因.
- 评估了RANBP2对BRAF类和非BRAF类CC细胞存活的关键性.
- 分析了RANBP2抑制对细胞分裂和微管体动态的影响.
- 在体外和体内对BRAF类CCs的敏感性进行了评估.
主要成果:
- 确定RANBP2对于BRAF类CC细胞的生存至关重要,而非非BRAF类CC细胞.
- 抑制RANBP2诱导了线粒细胞缺陷和细胞死亡,特别是在类似BRAF的CC中.
- RANBP2沉默导致了动脉管外生长的减少,导致螺旋的干扰.
- 与非BRAF类CC相比,BRAF类CC对维诺尔宾的敏感性显著增加.
结论:
- 在BRAF类结肠癌中,RANBP2是关键的生存因子.
- 该机制涉及RANBP2在维持适当的微管动力学和线粒细胞进展方面的作用.
- 维诺雷尔宾是一种有前途的向治疗药物,用于BRAF类结肠癌患者.
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