YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma
YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma
复制标题
DOI：
10.1126/sciadv.aay3324
复制
发表时间：
2020-03-01
期刊：
影响因子：
13.6
通讯作者：
Suzuki, Akira
中科院分区：
文献类型：
--
作者：
Omori, Hirofumi;Nishio, Miki;Suzuki, Akira
头颈部鳞状细胞癌（HNSCC）是世界上第六大常见癌症，患者预后较差。在这里，我们提供的数据表明YAP1可能是口腔鳞状细胞癌（OSCC）的发病和进展的强大驱动因素，OSCC是HNSCC的主要亚型。舌特异性缺失Mob1a/b并因此内源性YAP1过度激活的小鼠发生了惊人的快速和高度可重复性的肿瘤发生，在2周内发展为舌原位癌，在4周内发展为侵袭性SCC。在人类中，癌前舌发育不良显示YAP1激活与患者生存率降低相关。在OSCC中突变的分子组合可能会增加并维持YAP1的激活，直至致癌。引人注目的是，siRNA或YAP1的药理学抑制可在体外和体内阻断小鼠OSCC的发生。我们的工作证明靶向YAP1作为OSCC和HNSCC的治疗是合理的，我们的小鼠模型代表了评估这些药物的有力工具。
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.