title: Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma.
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.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.|Medical Research Center, Guangxi Medical University, Nanning, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.|Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Head and Neck Surgery, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Xianjie
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D038702:Follistatin-Related Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D019139:Tumor Escape / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D038702:Follistatin-Related Proteins; D053583:Interleukin-1beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C448799:FSTL1 protein, human
keywords: epigenetic inactivation; follistatin-like 1; nasopharyngeal carcinoma; tumor immune evasion