Lei Liu, Wu Jinsheng, Gu Dianhua, Liu Hui, Wang Shaochuang
Department of Hepatobiliary & Pancreatic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6th of West Beijing Road, Huai'an, Jiangsu Province, 223300, People's Republic of China.
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200438, China.
Tumour Biol. 2016 Aug;37(8):11073-9. doi: 10.1007/s13277-016-4866-8. Epub 2016 Feb 23.
Dysregulation of Hippo-Yes-associate protein (YAP) signaling has important roles in the tumorigenesis of hepatocellular carcinoma (HCC). Our previous studies have shown that Cip1 interacting zinc finger protein 1 (CIZ1) activated YAP signaling in the HCC cells and promoted the growth and migration of cancer cells. However, the mechanisms for the activation of YAP signaling by CIZ1 are unknown. In this study, it was found that CIZ1 interacted with the transcriptional factor YAP in HCC cells. The nuclear matrix anchor domain of CIZ1 is responsible for its interaction with YAP. Moreover, CIZ1 enhanced the interaction between YAP and TEAD. Knocking down the expression of CIZ1 impaired the transcriptional activity as well as the biological functions of YAP. Taken together, our study demonstrated that CIZ1 is a positive regulator of YAP signaling, and CIZ1 might be a therapeutic target for HCC.
Hippo-Yes相关蛋白(YAP)信号失调在肝细胞癌(HCC)的肿瘤发生中起重要作用。我们之前的研究表明,Cip1相互作用锌指蛋白1(CIZ1)在肝癌细胞中激活YAP信号,并促进癌细胞的生长和迁移。然而,CIZ1激活YAP信号的机制尚不清楚。在本研究中,发现CIZ1在肝癌细胞中与转录因子YAP相互作用。CIZ1的核基质锚定结构域负责其与YAP的相互作用。此外,CIZ1增强了YAP与TEAD之间的相互作用。敲低CIZ1的表达会损害YAP的转录活性以及生物学功能。综上所述,我们的研究表明CIZ1是YAP信号的正调控因子,CIZ1可能是肝癌的治疗靶点。