Hippo信号通路在哺乳动物肝脏发育、动态平衡、再生和疾病中发挥非常重要的作用。大肿瘤抑制基因1/2（large tumor suppressor 1/2， LATS1/2）激酶是Hippo信号通路的关键激酶，可以磷酸化YES相关蛋白（yes-associated protein，YAP），从而调节YAP的核质定位和降解。本文采用CRISPR/Cas9方法构建慢病毒介导的Last1/2基因敲除的载体，通过包装、感染和嘌呤霉素筛选，获得LATS1/2部分敲除的人卵巢癌ES-2和H08910细胞，免疫印迹方法检测LATS1/2表达明显减少。细胞增殖实验检测LATS1/2缺失明显抑制ES-2和HO8910细胞增殖。软琼脂克隆形成实验表明，LATS1/2缺失抑制卵巢癌ES-2细胞的克隆形成能力。细胞划痕和Transwell实验证明，LATS1/2缺失明显抑制卵巢癌ES-2细胞迁移。流式细胞检测发现，LATS1/2敲除促进卵巢癌ES-2细胞凋亡并影响细胞周期。裸鼠成瘤实验表明，LATS1/2缺失明显抑制体内肿瘤组织增殖。分子机制研究表明， LATS1/2敲除促进卵巢癌ES-2细胞中胶原I型α1（collagen type I α1，ColIα1）基因表达量增加，在卵巢癌ES-2细胞中同时敲除LATS1/2和COL1A1，可以促进细胞克隆形成。综上结果，人卵巢癌ES-2细胞中LATS1/2缺失能促进COL1A1表达增加, 从而抑制细胞增殖、转移和克隆形成，并影响细胞周期和促进细胞凋亡
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