日本神户大学的研究人员发现,某些良性肿瘤发生癌变是由于良性肿瘤细胞内合成能量的线粒体功能减弱,这些细胞会分泌引发炎症和细胞增殖的两种蛋白质,从而导致癌变。研究人员之前已知线粒体异常与癌变有关联,这是首次在生物体内确认线粒体异常与癌变发生的生物机制,将有助于开发新的癌症疗法。

-2012年10月25日《自然》


中文翻译


【题目】线粒体缺陷通过果蝇中Hippo信号驱动非自主肿瘤进展

【译文】线粒体呼吸功能通常在人类癌症中受损。然而,线粒体紊乱促进肿瘤进展的机制还不清楚。本研究表明线粒体功能缺陷的果蝇成虫上皮可以连同致癌基因Ras诱导周围组织的肿瘤进展。我们的数据表明Ras活化和线粒体功能紊乱协调刺激产生活性氧,从而激活c-Jun氨基酸N末端激酶(JNK)通路。JNK与原癌基因Ras协同作用以使Hippo通路失活,引起其靶点Wingless(Wnt同源物)和Unpaired(IL-6同源物)的表达上调。Ras激活的细胞中线粒体功能紊乱进一步与具有正常线粒体功能的邻近细胞中Ras协同作用,使得表现出转移行为的良性肿瘤。我们的发现为由线粒体功能紊乱和原癌基因Ras驱动的无性系肿瘤进展提供了一种机制基础。

英文原稿


[Title]: Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila

[Authors]:Shizue Ohsawa,1 Yoshitaka Sato,1 Masato Enomoto,1 Mai Nakamura,1 Aya Betsumiya1 & Tatsushi Igaki1, 2

[Abstract]Mitochondrial respiratory function is frequently impaired in human cancers. However, the mechanisms by which mitochondrial dysfunction contributes to tumour progression remain elusive. Here we show in Drosophila imaginal epithelium that defects in mitochondrial function potently induce tumour progression of surrounding tissue in conjunction with oncogenic Ras. Our data show that Ras activation and mitochondrial dysfunction cooperatively stimulate production of reactive oxygen species, which causes activation of c-Jun amino (N)-terminal kinase (JNK) signalling. JNK cooperates with oncogenic Ras to inactivate the Hippo pathway, leading to upregulation of its targets Unpaired (an interleukin-6 homologue) and Wingless (a Wnt homologue). Mitochondrial dysfunction in Ras-activated cells further cooperates with Ras signalling in neighbouring cells with normal mitochondrial function, causing benign tumours to exhibit metastatic behaviour. Our findings provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras.

原文地址

http://www.nature.com/nature/journal/v490/n7421/full/nature11452.html

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