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核外TERT可以抵消氧化应激,并促进乳头甲状腺癌的进展
Marina Muzza1, Gabriele Pogliaghi1, Carla Colombo2
1Department of Endocrine and Metabolic Diseases, Endocrine Oncology Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy.
概括
超核TERT保护乳头甲状腺癌 (PTC) 细胞免受氧化压力,促进生存和进展. 针对这种非核定位可以为PTC提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- TERT的重新激活与皮肤状甲状腺癌 (PTC) 的不良结果相关.
- TERT表现出端粒外功能,包括对氧化应激 (OS) 的保护.
研究的目的:
- 为了调查 PTC 中的非核 TERT 定位.
- 阐明TERT在癌症进展中的核外功能的作用.
主要方法:
- 在OS下对K1 PTC电池线的TERT核出口进行分析.
- 利用TERT构造来定义核与线粒体定位.
- 研究了SRC激酶抑制剂PP2对TERT核出口的影响.
- 相关的TERT定位在39个具有遗传特征,OS,DNA损伤,亡和临床特征的PTC组织中.
主要成果:
- 在响应H2O2或BRAF抑制剂PLX4720诱导的OS时,TERT从核中导出.
- 超核TERT减少了线粒体OS,并诱导了线粒体碎片化.
- 有限的线粒体TERT降低了增殖,迁移,AKT酸化和糖解,同时增加了DNA损伤和p21表达.
- 在PTC组织中,线粒体/核TERT分数与OS和p21表达相反相关,与瘤持久性相关.
结论:
- 超核TERT减轻了过度的OS,提高了癌细胞的存活率.
- 超核TERT局部化是PTC进展的潜在标志物.
- 超核TERT代表了PTC的潜在治疗目标.
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