Development of a new therapeutic tool against malignant mesothelioma

恶性间皮瘤（MM）是一种非常具有侵袭性的肿瘤，目前还没有针对这种致命疾病的有效化疗药物或分子靶向试剂。在这个项目中，我们进行了实验，以开发一种新的治疗模式对MM。由于MM显示频繁失活的p16INK4a肿瘤抑制基因，我们采用了一种功能性肽，这是透过细胞膜和恢复p16功能。我们发现这种肽非常有效和特异地诱导MM细胞凋亡，这似乎有望成为一种新的治疗工具。此外，我们还分析了雅普癌基因产物，其被组成性激活并导致MM细胞的更多恶性表型。我们阐明了TEAD家族转录因子的哪些成员，雅普结合伴侣，在MM细胞增殖失调中是重要的。这些发现对于开发一种新的策略来调节雅普蛋白作为MM的治疗方式是非常有指示性的。

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.