YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma
Hirofumi Omori, Miki Nishio, Muneyuki Masuda, Yosuke Miyachi, Fumihito Ueda, Takafumi Nakano, Kuniaki Sato, Koshi Mimori, Kenichi Taguchi, Hiroki Hikasa, Hiroshi Nishina, Hironori Tashiro, Tohru Kiyono, Tak W. Mak, Kazuwa Nakao, Takashi Nakagawa, Tomohiko Maehama, Akira Suzuki
Abstract
and thus endogenous YAP1 hyperactivation underwent surprisingly rapid and highly reproducible tumorigenesis, developing tongue carcinoma in situ within 2 weeks and invasive SCC within 4 weeks. In humans, precancerous tongue dysplasia displays YAP1 activation correlating with reduced patient survival. Combinations of molecules mutated in OSCC may increase and sustain YAP1 activation to the point of oncogenicity. Strikingly, siRNA or pharmacological inhibition of YAP1 blocks murine OSCC onset in vitro and in vivo. Our work justifies targeting YAP1 as therapy for OSCC and perhaps HNSCC, and our mouse model represents a powerful tool for evaluating these agents.