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14-3-3ζ Regulates Immune Response through Stat3 Signaling in Oral Squamous Cell Carcinoma

Ectopic expression of 14-3-3ζ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of 14-3-3ζ in the regulation of interactions between tumor cells and the immune system has not been previously repo...

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Published in:Molecules and Cells 2015, 38(2), , pp.112-121
Main Authors: Han, Xinguang, Han, Yongfu, Jiao, Huifeng, Jie, Yaqiong
Format: Article
Language:English
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Summary:Ectopic expression of 14-3-3ζ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of 14-3-3ζ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how 14-3-3ζ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that 14-3-3ζ is overexpressed. In OSCC cells, 14-3-3ζ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, 14-3-3ζ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Furthermore, supernatants from 14-3-3ζ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with 14-3-3ζ and its disruption relieved the inhibition induced by 14-3-3ζ in tumor inflammation. Taken together, our studies provide evidence that 14-3-3ζ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.
ISSN:0219-1032
1016-8478
0219-1032
DOI:10.14348/molcells.2015.2101