title: STAT3 signal transduction through interleukin-22 in oral squamous cell             carcinoma.
abstract: Interleukin (IL)-22 is a member of the IL-10 family. Its main targets are             epithelial cells, not immune cells. We examined IL-22 signal transduction in oral             squamous cell carcinoma (OSCC) cells. Immunohistochemical staining revealed that             IL-22R was expressed more highly in OSCC compared to normal regions. An IL-22R             signal was also observed in metastatic OSCC cells in the lymph node. RT-PCR showed             that the human OSCC cell lines MISK81-5, HSC-3, HSC-4, SAS and SQUU-B expressed             IL-22 receptor chains. Immunoblotting showed that IL-22 induced a transient tyrosine             phosphorylation of STAT3 (pY705-STAT3) in MISK81-5 cells. The change in the serine             phosphorylation of STAT3 was subtle during the examination periods. Simultaneously,             pY705-STAT3 activation in HSC-3 cells was undetectable after IL-22 stimulation.             Immunocytochemistry demonstrated that IL-22 induced the translocation of phosphorylated             STAT3 into the nucleus of MISK81-5 cells. IL-22 temporarily upregulated the expression             of anti-apoptotic and mitogenic genes such as Bcl-x, survivin and c-Myc, as well             as SOCS3. IL-22 transiently activated ERK1/2 and induced a delayed phosphorylation             of p38 MAP kinase, but negligibly involved the activation of NF-κB in MISK81-5             cells. MISK81-5 and SQUU-B cells treated with IL-22 showed mild cellular proliferation.             MISK81-5, HSC-4 and SAS cells treated with IL-22 downregulated the keratinocyte             differentiation-related genes compared with unstimulated cells. Conversely, STAT3             suppression by STAT3 siRNA strongly disrupted the downregulation of these genes             by IL-22, but it did not significantly affect the activation of ERK1/2 by IL-22.             The OSCC cells used in this study upregulated the expression of SERPINB3/4 (SCCA1/2),             well-known SCC markers, following treatment with IL-22. These results indicate             that IL-22 differentially activates the STAT3 signaling system depending on the             type of OSCC. IL-22 may therefore play a role in tumor growth, cell differentiation             and progression through STAT3-dependent and -independent pathways.
authors.affiliation: Laboratory of Oral Pathology and Medicine, Division of Maxillofacial                     Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University,                     Fukuoka 812-8582, Japan.
authors.forename: Lutfun
authors.initials: L
authors.lastname: Naher
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiyoshima
authors.forename: Ieyoshi
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.forename: Kengo
authors.initials: K
authors.lastname: Nagata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yukiko F
authors.initials: YF
authors.lastname: Ookuma
authors.forename: Satoru
authors.initials: S
authors.lastname: Ozeki
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; D007378:Interleukins; D016328:NF-kappa B; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D015843:Serpins; D000097043:Interleukin-22; C415369:interleukin-22 receptor; C051072:squamous cell carcinoma-related antigen