Narciclasine is a novel YAP inhibitor that disturbs interaction between YAP and TEAD4
Narciclasine is a novel YAP inhibitor that disturbs interaction between YAP and TEAD4
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DOI：
10.1016/j.bbadva.2021.100008
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发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Itoh, Susumu
中科院分区：
文献类型：
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作者：
Kawamoto, Rie;Nakano, Naoko;Itoh, Susumu
是相关蛋白（雅普）参与发育、细胞生长、细胞大小和稳态，并且在各种癌症的进展中起关键作用。其中，雅普的组成性激活通常可以在恶性间皮瘤中观察到，恶性间皮瘤由于Hippo通路的失活而在胸膜、腹膜和心包中产生。然而，迄今为止，只有疗效较差的治疗方法，如化疗、放疗和手术可用于恶性间皮瘤患者。在这项研究中，我们确定了那昔克拉新作为一种新的雅普抑制剂，防止雅普与TEAD 4相互作用，因为它与TEAD 4竞争结合雅普。此外，那昔克拉新除了抑制恶性间皮瘤NCI-H290细胞在裸鼠体内的生长外，还能干扰其生长和集落形成。因此，那昔克拉新可能是一种潜在的种子，一种新的抗肿瘤药物，对恶性间皮瘤和其他癌症，其中观察到的过度激活和/或过表达的雅普。
Yes -associated protein (YAP) is involved in development, cell growth, cell size, and homeostasis and plays a key role in the progression of various cancers. Among them, constitutive activation of YAP can often be observed in malignant mesothelioma, which arises in the pleura, peritoneum, and pericardium because of inactivation of the Hippo pathway. To date, however, only less -effective treatments such as chemotherapy, radiation therapy, and surgery are available for patients with malignant mesothelioma. In this study, we identified narciclasine as a novel YAP inhibitor that prevents YAP from interacting with TEAD4 because it competes with TEAD4 for binding to YAP. Furthermore, narciclasine could perturb the cell growth and colony formation of malignant mesothelioma NCI -H290 cells in addition to inhibiting their growth in nude mice. Therefore, narciclasine might be a potential seed for a novel antitumor drug against malignant mesothelioma and other cancers in which hyperactivation and/or overexpression of YAP are observed.