Narciclasine is a novel YAP inhibitor that disturbs interaction between YAP and TEAD4
Rie Kawamoto,
Naoko Nakano,
Haruka Ishikawa,
Etsu Tashiro,
Waka Nagano,
Keigo Sano,
Miki Irie,
Mariko Ikuta,
Fukuko Kishi,
Takahisa Nakane,
Mikihiko Naito,
Susumu Itoh
Affiliations
Rie Kawamoto
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Naoko Nakano
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Haruka Ishikawa
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Etsu Tashiro
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Waka Nagano
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Keigo Sano
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Miki Irie
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Mariko Ikuta
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Fukuko Kishi
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
Takahisa Nakane
Laboratory of Natural Products Chemistry, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan
Mikihiko Naito
Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-9501, Japan
Susumu Itoh
Laboratory of Biochemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan; Corresponding author at: Susumu Itoh, Laboratory of Biochemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
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.
