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癌症中的FGFR3-TACC3基因融合的代谢功能
Véronique Frattini1, Stefano M Pagnotta1,2, Tala1
1Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.
Nature
|January 12, 2018
概括
通过激活线粒体呼吸,FGFR3-TACC3 (F3-T3) 基因融合驱动癌症. 针对这种代谢途径为F3-T3阳性瘤提供了新的治疗策略.
科学领域:
- 癌症学
- 分子生物学
- 癌症新陈代谢
背景情况:
- 染色体转移产生瘤基因融合是癌症治疗的关键目标.
- FGFR3-TACC3 (F3-T3) 融合是各种癌症中发现的致癌驱动因素,包括质母细胞瘤.
- F3-T3聚变的下游信号通路在很大程度上是未知的.
研究的目的:
- 阐明由F3-T3融合激活的致癌信号通路.
- 调查线粒体功能在F3-T3驱动的瘤发生中的作用.
- 在F3-T3阳性癌症中发现潜在的治疗漏洞.
主要方法:
- 具有F3-T3融合的人类瘤的转录概况.
- 分析线粒体功能和氧化代谢.
- 研究F3-T3-PIN4信号轴及其下游影响.
主要成果:
- F3-T3融合与被激活的线粒体功能特征的转录子组相关.
- 激活氧化化和线粒体生物发生,从而对代谢抑制剂产生敏感性.
- F3-T3-PIN4轴促进过氧体生物发生和蛋白质合成,通过活性氧物种汇聚到PGC1α.
结论:
- F3-T3阳性瘤对线粒体呼吸的生长有很大的依赖.
- 通过F3- T3介导的线粒体代谢激活是一个重要的治疗机会.
- 了解F3-T3融合的代谢回路可以了解癌症的发展和治疗.
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