Xiao Meng, Yan Ming, Zhang Jianjun, Xu Qin, Qi Shengcai, Wang Xu, Chen Wantao
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China; Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, China.
Exp Cell Res. 2017 Apr 1;353(1):46-53. doi: 10.1016/j.yexcr.2017.03.005. Epub 2017 Mar 6.
Our previous studies have identified that CD166 works as a cancer stem-like cell (CSC) marker in epithelial cancers with a large repertoire of cellular functions. However, the post-translational regulatory mechanisms underlying CD166 turnover remain elusive. Several independent studies have reported that E3 ubiquitin ligase CHIP revealed significant biological effects through ubiquitin proteasome pathway on some kinds of malignant tumors. With analyzing the effects of CHIP expressions on stem-like cell populations, we found that CHIP represses CSC characteristics mainly targeting the CSC related protein CD166 in head and neck cancer (HNC). To investigate the role and relationship between CD166 and CHIP, HNC tissues and cell lines were used in this study. A significant negative correlation was observed between the expression levels of CHIP and CD166 in HNC patient samples. We also found that CHIP directly regulates the stability of CD166 protein through the ubiquitin proteasome system, which was also identified participating in the regulation of CSC behaviors in HNCs. Our findings demonstrate that CHIP-CD166-proteasome axis participates in regulating CSC properties in HNCs, suggesting that the regulation of CD166 by CHIP could provide new options for diagnosing and treating in the patients with HNCs.
我们之前的研究已经确定，CD166作为上皮癌中具有多种细胞功能的癌症干细胞（CSC）标志物。然而，CD166周转的翻译后调控机制仍然不清楚。几项独立研究报告称，E3泛素连接酶CHIP通过泛素蛋白酶体途径对某些恶性肿瘤显示出显著的生物学效应。通过分析CHIP表达对干细胞样细胞群体的影响，我们发现CHIP主要通过靶向头颈部癌（HNC）中与CSC相关的蛋白CD166来抑制CSC特征。为了研究CD166与CHIP之间的作用及关系，本研究使用了HNC组织和细胞系。在HNC患者样本中，观察到CHIP和CD166的表达水平之间存在显著的负相关。我们还发现，CHIP通过泛素蛋白酶体系统直接调节CD166蛋白的稳定性，这也被确定参与了HNC中CSC行为的调控。我们的研究结果表明，CHIP-CD166-蛋白酶体轴参与调节HNC中的CSC特性，这表明CHIP对CD166的调节可为HNC患者的诊断和治疗提供新的选择。
