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

[ Vol. 20 , Issue. 8 ]

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*Pages 624-637 (14)

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.

Affiliation:

Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008

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