title: IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway.
abstract: NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non-cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed. Furthermore, IL-8 stimulated the proliferation of HNSCC cells (SCC4, SCC9 and SCC25) but not dysplastic oral mucosa DOK cells. Exposure to IL-8 increased the clonogenicity of HNSCC cells. IL-8 siRNA inhibited cell proliferation and cell colony formation, suggesting that IL-8 is involved in HNSCC cancer progression. The expressions of CXCR1 and CXCR2 were higher in HNSCC tissue than in NCMT. HNSCC cells that were exposed to IL-8 exhibited higher expression of CXCR1/2 than did controls. The blocking of IL-8 by siRNA reduced CXCR1/2 expression in HNSCC cells, suggesting that the cancer progression of HNSCC cells that is induced by IL-8 depends on CXCR1/2. Additionally, IL-8 is associated with increased NOD1 and RIP2 expression and reduced NOD2 expression in three types of HNSCC cells. The blocking of IL-8 by siRNA reduces IL-8, NOD1 and RIP2 expressions in HNSCC cells, but not the level of NOD2. These results suggest that IL-8 has an important role in HNSCC progression via a CXCR1/2-meidated NOD1/RIP2 signaling pathway.
authors.affiliation: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Leong-Perng
authors.initials: LP
authors.lastname: Chan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ling-Feng
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Chiang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ka-Wo
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
authors.affiliation: Department of Cosmetic Science and Institute of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Liang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2
keywords: HNSCC; IL-8; NOD1; cancer progression