水仙环素是一种新型的YAP抑制剂，它会干扰YAP与TEAD4之间的相互作用。
Narciclasine is a novel YAP inhibitor that disturbs interaction between YAP and TEAD4.
作者信息
Kawamoto Rie, Nakano Naoko, Ishikawa Haruka, Tashiro Etsu, Nagano Waka, Sano Keigo, Irie Miki, Ikuta Mariko, Kishi Fukuko, Nakane Takahisa, Naito Mikihiko, Itoh Susumu
机构信息
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Laboratory of Natural Products Chemistry, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan.
出版信息
BBA Adv. 2021 Mar 27;1:100008. doi: 10.1016/j.bbadva.2021.100008. eCollection 2021.
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.
Yes相关蛋白（YAP）参与发育、细胞生长、细胞大小和体内平衡，并在多种癌症的进展中起关键作用。其中，YAP的组成性激活在恶性间皮瘤中经常可见，恶性间皮瘤由于Hippo通路失活而发生于胸膜、腹膜和心包。然而，迄今为止，对于恶性间皮瘤患者，仅化疗、放疗和手术等效果欠佳的治疗方法可用。在本研究中，我们鉴定出水仙环素是一种新型YAP抑制剂，它可阻止YAP与TEAD4相互作用，因为它与TEAD4竞争结合YAP。此外，水仙环素除了抑制恶性间皮瘤NCI-H290细胞在裸鼠体内的生长外，还可干扰其细胞生长和集落形成。因此，水仙环素可能是一种针对恶性间皮瘤和其他观察到YAP过度激活和/或过表达的癌症的新型抗肿瘤药物的潜在种子。
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