A positive feedback loop of IL-17B-IL-17RB activates ERK/β-catenin to promote lung cancer metastasis

Inflammation contributes to the development and progression of cancer. Interleukin-17 (IL-17) is an inflammatory cytokine that functions in inflammation and cancer, as well as several other cellular processes. In this study, we investigated the roles and the prognostic value of IL-17 and the IL-17 r...

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Bibliographic Details
Published in:	Cancer letters 2018-05, Vol.422, p.44-55
Main Authors:	Yang, Yi-Fang, Lee, Yi-Chen, Lo, Steven, Chung, Yi-Ning, Hsieh, Ya-Ching, Chiu, Wen-Chin, Yuan, Shyng-Shiou F.
Format:	Article
Language:	eng
Subjects:	Automation Breast cancer Cell migration Cell survival Chronic obstructive pulmonary disease Cytokines DNA microarrays ERK Extracellular signal-regulated kinase Feedback Feedback loops Gene expression IL-17B IL-17RB Inactivation Inflammation Interleukin 17 Kinases Ligands Liver cancer Lung cancer Lymph nodes Medical prognosis Medical research Metabolic pathways Metastases Metastasis Pathogenesis Patients Phosphorylation Positive feedback Prostate cancer Proteins Therapeutic applications Tumor cell lines Tumorigenesis β-Catenin
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Summary:	Inflammation contributes to the development and progression of cancer. Interleukin-17 (IL-17) is an inflammatory cytokine that functions in inflammation and cancer, as well as several other cellular processes. In this study, we investigated the roles and the prognostic value of IL-17 and the IL-17 receptor (IL-17R) in lung cancer. Gene expression microarray analysis followed by Kaplan-Meier survival curve showed that IL-17B was associated with poor patient survival, and IL-17B receptor (IL-17RB) was up-regulated in lung cancer tissue compared with normal tissue. Expression of IL-17RB was associated with lymph node metastasis and distant metastasis, as well as poor patient survival. IL-17RB overexpression significantly increased cancer cell invasion/migration and metastasis in vitro and in vivo. IL-17RB induced ERK phosphorylation, resulting in GSK3β inactivation and leading to β-catenin up-regulation. IL-17RB also participated in IL-17B synthesis via the ERK pathway. IL-17RB activation is required for IL-17B-mediated ERK phosphorylation. Taken together, IL-17B-IL-17RB signaling and ERK participate in a positive feedback loop that enhances invasion/migration ability in lung cancer cell lines. IL-17RB may therefore serve as an independent prognostic factor and a therapeutic target for lung cancer. •Up-regulated of IL-17RB correlates with poor clinical outcomes in lung cancer.•IL-17RB overexpression increased lung cancer cell invasiveness and metastasis.•IL-17RB activation is required for IL-17B-mediated ERK phosphorylation.•IL-17RB participated in IL-17B synthesis via the ERK pathway.
ISSN:	0304-3835 1872-7980