CD166 promotes cancer stem cell-like phenotype via the EGFR/ERK1/2 pathway in the nasopharyngeal carcinoma cell line CNE-2R

CD166 promotes cancer stem cell-like phenotype via the EGFR/ERK1/2 pathway in the nasopharyngeal carcinoma cell line CNE-2R
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CD166通过EGFR/ERK1/2通路在鼻咽癌细胞系CNE-2R中促进癌症干细胞样表型

DOI:
10.1016/j.lfs.2020.118983
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发表时间:
2021-01-04
期刊:
影响因子:
6.1
通讯作者:
Zhu, Xiaodong
Zhu, Xiaodong
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Xishan;Liang, Renba;Zhu, Xiaodong

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目的:探讨CD166在鼻咽癌放射抵抗细胞株CNE-2R肿瘤干细胞样表型中的作用及其机制。主要方法:通过慢病毒介导沉默CD166,建立CD166-shRNA-CNE-2R细胞系。采用RT-PCR和Western印迹方法检测CSC相关基因的表达及EGFR/ERK1/2信号转导通路。用球体形成实验评价CD166-shRNA-CNE-2R细胞的球体形成能力。通过裸鼠体内成瘤实验,发现CD166基因的表达下调抑制了肿瘤干细胞相关基因pEGFR和PERK的表达。CD166-shRNA细胞的球体形成能力和致瘤性显著降低。此外,EGF刺激的CD166-shRNA细胞通过激活EGFR/ERK1/2信号通路增加了CSC样特性。意义:CD166通过激活EGFR/ERK1/2信号通路在鼻咽癌中诱导CSCs的形成,这可能是鼻咽癌治疗策略的关键分子靶点。
Aims: The present study aimed to investigate the role and underlying mechanisms of CD166 in cancer stem cell-like (CSCs) phenotype of the radioresistant nasopharyngeal carcinoma cell CNE-2R.Main methods: Established CD166-shRNA- CNE-2R cell line by lentivirus-mediated silencing CD166. Then, CSC-related genes mRNAs and proteins, and EGFR/ERK1/2 signaling pathway were detected using RT-PCR and western blot. Sphere formation assay was performed to evaluate the sphere formation capacity in CD166-shRNA-CNE-2R cells. The tumorigenesis ability in vivo was examined in nude mice mode.Key findings: Downregulation of CD166 inhibited the expression of the CSC-related genes, pEGFR and pERK in vitro and vivo. The capacity to form spheres and tumorigenesis was significantly decreased in CD166-shRNA cells. Furthermore, EGF-stimulated CD166-shRNA cells exhibited an increase in CSC-like traits by activating EGFR/ERK1/2 signaling.Significance: CD166 induced CSCs formation by activating the EGFR/ERK1/2 signaling pathway in nasopharyngeal carcinoma, which may serve as a critical molecular target for NPC therapeutic strategies.