Nature：基因融合下游致癌信号被揭示

2018-01-04 海北 MedSci原创

染色体易位产生阅读框内致癌基因融合是靶向癌症治疗的一个成功的例子。研究人员之前已经报导了，3％的人类胶质母细胞瘤病例中含有FGFR3-TACC3（F3-T3）的基因融合。

染色体易位产生阅读框内致癌基因融合是靶向癌症治疗的一个成功的例子。研究人员之前已经报导了，3％的人类胶质母细胞瘤病例中含有FGFR3-TACC3（F3-T3）的基因融合。随后的研究报道了F3-T3在许多其他癌症中也具有相似的频率。这表明F3-T3是在所有肿瘤类型中都很常见的融合。 F3-T3融合蛋白是赋予FGFR抑制剂敏感性的有效癌基因，但是至今为止，其下游致癌信号通路仍然是未知的。

来自哥伦比亚大学医学中心的研究人员发现，在人类肿瘤中，F3-T3融合集群在转录子中，这些转录子作用于线粒体功能的激活。F3-T3激活氧化磷酸化和线粒体的生物合成，并诱导对氧化代谢抑制剂的敏感性。磷酸化肽PIN4的磷酸化是线粒体代谢激活的信号传导途径中的中间步骤。 F3-T3-PIN4轴能够触发过氧化物酶体的生物合成和新蛋白质的合成。合成代谢反应通过产生细胞内活性氧物质（其促使线粒体呼吸和肿瘤生长）聚集在PGC1α共激活物上。

这些数据解释了F3-T3参与的致癌循环，并且显示F3-T3阳性肿瘤依赖于线粒体呼吸，强调了该途径作为治疗F3-T3融合肿瘤的潜力。

原始出处：

Véronique Frattini et al. A metabolic function of FGFR3-TACC3 gene fusions in cancer. Nature, 2018; DOI: 10.1038/nature25171

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#插入话题

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2018-07-16 lvygwyt2790

#基因融合#

38 0
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2018-05-26 liye789132251

#Nat#

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2018-01-06 jambiya

#致癌#

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2018-01-06 licz0427

#融合#

24 0
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2018-01-05 方舒

学习

39 0
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2018-01-04 131****1460

学习了受益匪浅

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