Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.
Cancer stem-like cell related protein CD166 degrades through E3 ubiquitin ligase CHIP in head and neck cancer.
复制标题
头颈癌中癌症干细胞样细胞相关蛋白 CD166 通过 E3 泛素连接酶 CHIP 降解
DOI：
10.1016/j.yexcr.2017.03.005
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发表时间：
2017-04-01
影响因子：
3.7
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Xiao M;Yan M;Zhang J;Xu Q;Qi S;Wang X;Chen W
我们以前的研究已经确定，CD 166作为上皮癌中的癌症干细胞样细胞（CSC）标记物，具有大量的细胞功能。然而，CD 166周转的翻译后调控机制仍然难以捉摸。一些独立的研究表明，E3泛素连接酶CHIP通过泛素蛋白酶体途径对某些恶性肿瘤具有重要的生物学效应。通过分析CHIP表达对干细胞样细胞群体的影响，我们发现CHIP主要针对头颈癌（HNC）中CSC相关蛋白CD 166抑制CSC特性。为了研究CD 166与CHIP之间的作用和关系，本研究使用HNC组织和细胞系。在HNC患者样品中观察到CHIP和CD 166的表达水平之间显著负相关。我们还发现CHIP通过泛素蛋白酶体系统直接调节CD 166蛋白的稳定性，该系统也被证实参与了HNC中CSC行为的调节。我们的研究结果表明，CHIP-CD 166-蛋白酶体轴参与调节HNC中CSC的特性，表明CHIP对CD 166的调节可能为HNC患者的诊断和治疗提供新的选择。
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.