Oncotarget

Research Papers:

Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma

Xiaoying Zhou, Xue Xiao, Tingting Huang, Chunping Du, Shumin Wang, Yingxi Mo, Ning Ma, Mariko Murata, Bo Li, Wensheng Wen, Guangwu Huang, Xianjie Zeng & Zhe Zhang _

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Oncotarget. 2016; 7:16433-16444. https://doi.org/10.18632/oncotarget.7654

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Abstract

Xiaoying Zhou1,2,*, Xue Xiao1,*, Tingting Huang1, Chunping Du1, Shumin Wang1, Yingxi Mo1,3, Ning Ma4, Mariko Murata3, Bo Li1, Wensheng Wen1, Guangwu Huang1, Xianjie Zeng5, Zhe Zhang1

1Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China

2Medical Research Center, Guangxi Medical University, Nanning, China

3Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan

4Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Japan

5Department of Head and Neck Surgery, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, China

*These authors contributed equally to this work

Correspondence to:

Zhe Zhang, e-mail: zhangzhe@gxmu.edu.cn

Keywords: epigenetic inactivation, follistatin-like 1, tumor immune evasion, nasopharyngeal carcinoma

Received: July 29, 2015     Accepted: February 06, 2016     Published: February 24, 2016

ABSTRACT

Follistatin like-1 (FSTL1) is a secreted glycoprotein involved in a series of physiological and pathological processes. However, its contribution to the development of cancer, especially the pathogenesis of nasopharyngeal carcinoma (NPC), remains to be elucidated. We aimed to investigate the dysregulation of FSTL1 and its possible function in NPC. FSTL1 was frequently downregulated in NPC cell lines and primary tumor biopsies by promoter hypermethylation. Ectopic expression of FSTL1 significantly suppressed the colony formation, proliferation, migration and invasion ability of NPC cells and induced cell apoptosis. Overexpression of FSTL1 decreased the tumorigenicity of NPC cells in vivo. In addition, the proliferation of NPC cells in vitro was inhibited by treatment with soluble recombinant FSTL1 protein. The protein level of FSTL1 was decreased in primary NPC tumors and was associated with downregulated interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Furthermore, recombinant human FSTL1 protein induced secretion of IL-1β and TNF-α in macrophage cultures, therefore FSTL1 might activate macrophages and attenuate the immune evasion of NPC cells. In conclusion, the epigenetic downregulation of FSTL1 may suppress the proliferation and migration of NPC cells, leading to dysfunctional innate responses in surrounding macrophages.


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