Development of a new therapeutic tool against malignant mesothelioma

恶性间皮瘤（Malignant mesothelioma， MM）是一种侵袭性很强的肿瘤，目前尚无有效的化疗药物或分子靶向试剂治疗这种致命疾病。在这个项目中，我们进行了实验，以开发一种新的治疗MM的方法。由于MM表现出p16INK4a肿瘤抑制基因的频繁失活，我们采用了一种可穿透细胞膜并恢复p16功能的功能肽。我们发现该肽非常有效且特异性地诱导MM细胞凋亡，有望成为一种新的治疗工具。此外，我们还分析了YAP癌基因产物，它被组成性激活并导致MM细胞更多的恶性表型。我们澄清了TEAD家族转录因子的哪些成员，YAP结合伙伴，在失调的MM细胞增殖中是重要的。这些发现对开发一种新的策略来调节YAP蛋白作为MM的治疗方式非常有指示意义。

Malignant mesothelioma (MM) is a very aggressive tumor and, currently, there are no effective chemotherapeutic drugs or molecular-target reagents against this fatal disease. In this project, we performed experiments to develop a new therapeutic modality against MM. Since MM shows frequent inactivation of p16INK4a tumor suppressor gene, we employed a functional peptide which is permeable through the cell membrane and restores p16 function. We found that this peptide induced apoptosis of MM cells very effectively and specifically, which seemed promising to be a new therapeutic tool. Furthermore, we also analyzed YAP oncogene product, which is constitutively activated and leads to more malignant phenotypes of MM cells. We clarified which members of TEAD family transcription factors, YAP binding partners, were important in deregulated MM cell proliferation. These findings were very indicative to develop a new strategy to regulate YAP protein as a therapeutic modality of MM.