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Current Cancer Drug Targets

Author(s): Qiong Wu, Manlin Xiang, Kun Wang, Zhen Chen, Lu Long, Ya Tao, Yunlai Liang, Yahui Yan, Zhiqiang Xiao, Shiyang Qiu and Bin Yi*

DOI: 10.2174/1568009620666200424145122

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Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway

Page: [624 - 637] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

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<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis.

Conclusion: Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.

Keywords: Nasopharyngeal carcinoma, p62, metastasis, autophagy, autoantibody, ERK, EMT.

Graphical Abstract

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