Zhang Dexiang, Wang Yueqi, Dai Yuedi, Wang Jiwen, Suo Tao, Pan Hongtao, Liu Han, Shen Sheng, Liu Houbao
General Surgery Department, Zhongshan Hospital, General Surgery Institute, Fudan University, 180 Fenglin Rd., 200032, Shanghai, China.
Tumour Biol. 2015 Apr;36(4):2583-91. doi: 10.1007/s13277-014-2876-y. Epub 2014 Nov 28.
Gallbladder cancer (GBC) is one of the most common and aggressive diseases among the gastrointestinal tract malignancies, and the molecular mechanism underlying this disease remains largely unknown. CIZ1 (Cip1 interacting zinc finger protein 1), a binding partner of p21(Cip1/Waf1), has been found to be involved in the tumorigenesis recently. However, the expression pattern and biological functions of CIZ1 in the progression of GBC are not fully understood. In this study, it was found that the expression of CIZ1 was significantly elevated in GBC samples compared to their adjacent normal tissues. Moreover, overexpression of CIZ1 promoted the growth and migration of GBC cells, while knocking down the expression of CIZ1 inhibited the growth, migration, and tumorigenesis of GBC cells in vitro and in vivo. Mechanistically, CIZ1 was found to interact with TCF4 (T-cell factor) and activate beta-catenin/TCF signaling. Our study demonstrated that CIZ1 played an oncogenic role in the progression of GBC and CIZ1 might be a promising target for the treatment of GBC.
胆囊癌（GBC）是胃肠道恶性肿瘤中最常见且侵袭性最强的疾病之一，该疾病背后的分子机制在很大程度上仍不清楚。CIZ1（Cip1相互作用锌指蛋白1）是p21（Cip1/Waf1）的结合伴侣，最近发现它参与肿瘤发生。然而，CIZ1在GBC进展中的表达模式和生物学功能尚未完全了解。在本研究中，发现与相邻正常组织相比，CIZ1在GBC样本中的表达显著升高。此外，CIZ1的过表达促进了GBC细胞的生长和迁移，而敲低CIZ1的表达则在体外和体内抑制了GBC细胞的生长、迁移和肿瘤发生。机制上，发现CIZ1与TCF4（T细胞因子）相互作用并激活β-连环蛋白/TCF信号。我们的研究表明，CIZ1在GBC进展中起致癌作用，CIZ1可能是治疗GBC的一个有前景的靶点。
