Srivastava Ajay
Department of Biology and Biotechnology Center, Western Kentucky University, 1906 College Heights Boulevard, TCCW 351, Bowling Green, KY 42101, USA.
FEBS Open Bio. 2015 Aug 19;5:705-11. doi: 10.1016/j.fob.2015.07.005. eCollection 2015.
Malignant pleural mesothelioma (MPM) is an aggressive form of thoracic cancer with poor prognosis. While some studies have identified the molecular alterations associated with MPM, little is known about their role in MPM. For example, fragile X mental retardation (FMR) gene is up-regulated in MPM but its role in MPM is unknown. Here, utilizing Drosophila genetics, I investigate the possible role FMR may be playing in MPM. I provide evidence which suggests that FMR may contribute to tumorigenesis by up-regulating a matrix metalloprotease (MMP) and by degrading the basement membrane (BM), both important for tumor metastasis. I also demonstrate a novel link between FMR and the JNK pathway and suggest that the effects of FMR in MPM could in part be mediated by up-regulation of the JNK pathway.
恶性胸膜间皮瘤(MPM)是一种侵袭性胸段癌症,预后较差。虽然一些研究已经确定了与MPM相关的分子改变,但对它们在MPM中的作用知之甚少。例如,脆性X智力低下(FMR)基因在MPM中上调,但其在MPM中的作用尚不清楚。在这里,利用果蝇遗传学,我研究了FMR在MPM中可能发挥的作用。我提供的证据表明,FMR可能通过上调基质金属蛋白酶(MMP)和降解基底膜(BM)来促进肿瘤发生,这两者对肿瘤转移都很重要。我还证明了FMR与JNK通路之间的新联系,并表明FMR在MPM中的作用可能部分是由JNK通路的上调介导的。