Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway
Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway
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DOI：
10.2174/1568009620666200424145122
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发表时间：
2020-01-01
影响因子：
3
通讯作者：
Yi, Bin
中科院分区：
文献类型：
--
作者：
Wu, Qiong;Xiang, Manlin;Yi, Bin
背景：越来越多的证据表明p62在肿瘤发生中起重要作用。目的：探讨p62蛋白在鼻咽癌发生、发展中的作用，为临床治疗鼻咽癌提供理论依据。方法：采用免疫荧光染色、Western blotting和免疫组化等方法，检测鼻咽癌组织中p62蛋白的表达，分析p62蛋白在鼻咽癌发生、发展中的作用。随后，进行细胞活力、集落形成、迁移、侵袭和自噬测定。ELISA法检测血清中抗p62自身抗体。结果：p62在鼻咽癌组织中表达明显上调，与临床病理参数相关。p62在鼻咽癌细胞系中呈高表达，尤其是在高转移的5- 8 F细胞中。在体外，下调p62抑制5- 8 F细胞的增殖、克隆形成能力、自噬、迁移和侵袭，而p62过表达在6- 10 B细胞中导致相反的效果。此外，我们证实p62通过激活ERK（细胞外信号调节激酶，ERK）促进NPC细胞增殖、迁移和侵袭。p62高表达与淋巴结转移、远处转移有关（P
Background: Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated.Objective: To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma.Methods: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters.Results: We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal-regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P