Over the past decades, the Hippo has been established as a crucial pathway involved in organ size control and cancer suppression. Dysregulation of Hippo signaling and hyperactivation of its downstream effector YAP are frequently associated with various human cancers. However, the underlying significance of such YAP activation in cancer development and therapy has not been fully characterized. In this study, we reported that the Hippo signaling deficiency can lead to a YAP-dependent oncogene addiction for cancer cells. Through a clinical compound library screen, we identified histone deacetylase (HDAC) inhibitors as putative inhibitors to suppress YAP expression. Importantly, HDAC inhibitors specifically targeted the viability and xenograft tumor growth for the cancer cells in which YAP is constitutively active. Taken together, our results not only establish an active YAP-induced oncogene addiction in cancer cells, but also lay the foundation to develop targeted therapies for the cancers with Hippo dysfunction and YAP activation.

中文翻译：

---

河马信号功能障碍诱导癌细胞成瘾于YAP。

在过去的几十年中，河马已被确立为参与器官大小控制和癌症抑制的重要途径。Hippo信号调节异常及其下游效应物YAP过度活化通常与各种人类癌症有关。但是，这种YAP激活在癌症发展和治疗中的根本意义尚未得到充分表征。在这项研究中，我们报道了河马信号缺陷可以导致癌细胞依赖YAP的致癌基因成瘾。通过临床化合物库筛选，我们确定了组蛋白脱乙酰基酶（HDAC）抑制剂作为抑制YAP表达的推定抑制剂。重要的是，HDAC抑制剂专门针对其中YAP具有组成性活性的癌细胞的生存力和异种移植肿瘤的生长。在一起