极光激酶A通过激活喉鳞状细胞癌中休眠细胞诱导化疗耐药。

Aurora kinase A induces chemotherapy resistance through revival of dormant cells in laryngeal squamous cell carcinoma.

作者信息

Yang Li-Yun, Shan Ya-Min, Zhang Yi, Zhou En-Hui, Chen Xiao-Ping, Zhang Hao

机构信息

Department of Otolaryngology, Gongli Hospital, The Second Military Medical University, Shanghai, China.

Department of Otolaryngology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

出版信息

Head Neck. 2019 Jul;41(7):2239-2248. doi: 10.1002/hed.25689. Epub 2019 Feb 1.

DOI:10.1002/hed.25689

PMID:30706572

Abstract

BACKGROUND

Chemotherapy resistance was an important tumor metastasis mechanism.

METHODS

Cell Counting Kit-8 assay and plate colony formation assay were applied to examine the proliferation of laryngeal squamous cell carcinoma (LSCC). Immunofluorescent staining and Western blotting were carried out to show the expression of related proteins. Wound healing, migration, and invasion assays were used to examine the mobility, migration, and invasion of LSCC.

RESULTS

Downregulated Aurora kinase A (AURKA) increased chemotherapy sensitivity and reduced the ability of mobility, migration, and invasion of Hep2 cells, while upregulated AURKA possessed opposite results. Hep2/5-Fu cells possessed dormancy-like properties and upregulated AURKA in Hep2/5-Fu cells (Hep2/5-Fu/AURKA cells) revived dormant state. Furthermore, Erk1/2 was restrained in Hep2/5-Fu cells and activated in Hep2/5-Fu/AURKA cells. Moreover, Erk1/2 accelerated the ability of mobility, migration, and invasion in Hep2/5-Fu/AURKA cells.

CONCLUSION

AURKA activated dormant state to induce chemotherapy resistance and promoted metastasis of LSCC through Erk1/2 pathway.

摘要

背景

化疗耐药是一种重要的肿瘤转移机制。

方法

采用细胞计数试剂盒-8法和平板克隆形成试验检测喉鳞状细胞癌（LSCC）的增殖情况。进行免疫荧光染色和蛋白质免疫印迹法以显示相关蛋白的表达。采用伤口愈合、迁移和侵袭试验检测LSCC的移动性、迁移和侵袭能力。

结果

下调极光激酶A（AURKA）可提高化疗敏感性，并降低Hep2细胞的移动性、迁移和侵袭能力，而上调AURKA则产生相反的结果。Hep2/5-Fu细胞具有类似休眠的特性，Hep2/5-Fu细胞（Hep2/5-Fu/AURKA细胞）中上调的AURKA使休眠状态复苏。此外，Erk1/2在Hep2/5-Fu细胞中受到抑制，而在Hep2/5-Fu/AURKA细胞中被激活。此外，Erk1/2增强了Hep2/5-Fu/AURKA细胞的移动性、迁移和侵袭能力。