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.
Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network