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 Wah Mak, Kazuwa Nakao, Takashi Nakagawa, Tomohiko Maehama, Akira Suzuki

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6 Citations (Scopus)

Abstract

Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common group of cancers in the world, and patients have a poor prognosis. Here, we present data indicating that YAP1 may be a strong driver of the onset and progression of oral SCC (OSCC), a major subtype of HNSCC. Mice with tongue-specific deletion of Mob1a/b 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.

Original languageEnglish
Article numbereaay3324
JournalScience Advances
Volume6
Issue number12
DOIs
Publication statusPublished - 2020

ASJC Scopus subject areas

  • General

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    Omori, H., Nishio, M., Masuda, M., Miyachi, Y., Ueda, F., Nakano, T., Sato, K., Mimori, K., Taguchi, K., Hikasa, H., Nishina, H., Tashiro, H., Kiyono, T., Mak, T. W., Nakao, K., Nakagawa, T., Maehama, T., & Suzuki, A. (2020). YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma. Science Advances, 6(12), [eaay3324]. https://doi.org/10.1126/sciadv.aay3324