研究人员之前已知线粒体异常与癌变有关联
日本神户大学的一个研究小组近日英国《自然》杂志网络版上报告说，他们利用果蝇进行实验，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。
报告指出，研究人员之前已知线粒体异常与癌变有关联，但这次是首次在生物体内确认这一机制。如果能够遏制这种机制，将有助于开发新的癌症治疗方法。
研究小组在果蝇的眼球组织内激活与肿瘤发病有关的Ras基因，制作出良性肿瘤。这种良性肿瘤本身不会扩散和转移，但是当良性肿瘤细胞的一部分发生基因变异，导致细胞内合成能量的线粒体功能减弱后，研究人员发现良性肿瘤细胞发生癌变，并具有扩散和转移的能力。
研究小组还发现，线粒体功能减弱的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。
研究小组负责人井垣达吏指出：“研究人员以前一直不清楚癌细胞中线粒体功能减弱对癌症发病的具体作用。此次研究表明，线粒体功能减弱有可能在癌症的复发和转移中发挥重要作用。”
良性肿瘤是机体内某些组织的细胞发生异常增殖，呈膨胀性生长，但生长比较缓慢。良性肿瘤绝大多数不会恶变，很少复发，对机体影响较小。但有些良性肿瘤会发生癌变。
Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila
Shizue Ohsawa, Yoshitaka Sato, Masato Enomoto, Mai Nakamura, Aya Betsumiya & Tatsushi Igaki
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.
文献链接：Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila
