The biological roles of YAP in malignant mesothelioma proliferation and invasion

我们最近发现恶性间皮瘤细胞系经常携带与Hippo肿瘤抑制通路相关的基因突变。Hippo通路的失调导致转录共激活因子yes相关蛋白（YAP）和带pdz结合基序的YAP类转录共激活因子（TAZ）的激活。然而，YAP/TAZ对MM细胞生长或运动的具体作用尚不清楚。为了研究YAP/TAZ在MM细胞发育中的生物学作用，我们在MM细胞中建立了慢病毒介导的YAP或TAZ敲除系统，并利用寡核苷酸芯片分析了细胞生长、运动和基因表达模式的变化。SiRNA介导的YAP/TAZ在MM细胞系中的减少抑制细胞增殖和运动。我们还发现，通过YAP/TAZ敲低，一些参与细胞增殖、凋亡和细胞骨架的基因被解除调控。我们的研究结果将为间皮瘤的发展提供新的见解，并为开发新的间皮瘤分子靶向治疗提供一些线索。

We recently revealed malignant mesothelioma cell lines frequently harbor mutations of the genes associated with Hippo tumor suppressor pathway. Dysregulation of Hippo pathway leads to activation of a transcriptional co-activator Yes-associated protein (YAP) and the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ). However the detailed function of YAP/TAZ on MM cell growth or motility remains unclear. To investigate the biological roles of YAP/TAZ in MM development, we generated lentivirus mediated YAP or TAZ knock-down system in MM cells, and analyzed the changes in cell growth, motility, and the gene expression patterns with oligonucleotide microarrays. SiRNA mediated reduction of YAP/TAZ in MM cell lines suppress cell proliferation and motility. We also detected the deregulation of several genes involved in cell proliferation, apoptosis, and cytoskeleton by YAP/TAZ knockdown. Our results will provide new insights into development of mesothelioma, and give some clues to developing a new molecular target therapy for mesothelioma.