國家衛生研究院 NHRI:Item 3990099045/9353
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    題名: Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
    其他題名: Interleukin-1 β transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
    作者: Lee, CH;Syu, SH;Liu, KJ;Chu, PY;Yang, WC;Lin, P;Shieh, WY
    貢獻者: National Institute of Cancer Research;National Institute of Environmental Health Sciences
    摘要: Hyperactivation of the epidermal growth factor receptor (EGFR) pathways and chronic inflammation are common characteristics of oral squamous cell carcinoma (OSCC). Previously, we reported that OSCC cells secrete interleukin-1 beta (IL-1beta), which promotes the proliferation of the oral premalignant cell line, DOK, and stimulates DOK and OSCC cells to produce the chemokine CXCL1. CXCL1 functions through CXCR2, a G protein-coupled receptor that transactivates EGFR in ovarian and lung cancers. We hypothesized that IL-1beta transactivates EGFR through the CXCL1-CXCR2 axis in OSCC. In this study, we demonstrated that tyrosine phosphorylation of EGFR is crucial for the IL-1beta-mediated proliferation and subsequent bromodeoxyuridine (BrdU) incorporation of DOK cells because the EGFR inhibitors AG1478 and erlotinib inhibit these abilities in a dose-dependent manner. Addition of IL-1beta instantly enhanced CXCL1 expression and secretion (within 15 min) in the DOK and OSCC cell lines. Furthermore, tyrosine phosphorylation of EGFR was significantly enhanced in DOK (1 h) and OSCC (20 min) cell lines after IL-1beta treatment, and both cell lines were inhibited on the addition of an IL-1 receptor antagonist (IL-1Ra). CXCL1 treatment resulted in EGFR phosphorylation, whereas the knockdown of CXCL1 expression by lentivirus-mediated shRNA or the addition of the CXCR2 antagonist SB225002 dramatically reduced IL-1beta-mediated EGFR phosphorylation and proliferation of DOK cells. Neutralizing antibodies against IL-1beta or CXCL1 markedly inhibited the constitutive or IL-1beta-induced tyrosine phosphorylation of EGFR in OSCC cells. IL-1beta transactivates EGFR through the CXCL1-CXCR2 axis, revealing a novel molecular network in OSCC that is associated with autocrine IL-1beta and EGFR signaling.
    日期: 2015-11
    關聯: Oncotarget. 2015 Nov;6(36):38866-38880.
    Link to: http://dx.doi.org/10.18632/oncotarget.5640
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000366114000034
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84948799145
    顯示於類別:[李家惠] 期刊論文
    [劉柯俊] 期刊論文
    [林嬪嬪] 期刊論文

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