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

Yang, Y.-F., Lee, Y.-C., Lo, S. , Chung, Y.-N., Hsieh, Y.-C., Chiu, W.-C. and Yuan, S.-S. F. (2018) A positive feedback loop of IL-17B-IL-17RB activates ERK/β-catenin to promote lung cancer metastasis. Cancer Letters, 422, pp. 44-55. (doi: 10.1016/j.canlet.2018.02.037) (PMID:29496538)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by grants from Kaohsiung Medical University Hospital (KMUH105- 5R32), Kaohsiung Medical University (Aim for the Top Journals Grant, KMU-TP105D10, KMU-DT106004) and National Science Council (MOST 106-2314-B-037-005-MY2).
Keywords:ERK, IL-17B, IL-17RB, lung cancer, metastasis.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hsieh, Dr Ya-Ching and Lo, Mr Steven
Authors: Yang, Y.-F., Lee, Y.-C., Lo, S., Chung, Y.-N., Hsieh, Y.-C., Chiu, W.-C., and Yuan, S.-S. F.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Letters
Publisher:Elsevier
ISSN:0304-3835
ISSN (Online):1872-7980
Published Online:26 February 2018
Copyright Holders:Copyright © 2018 Elsevier B.V.
First Published:First published in Cancer Letters 422: 44-55
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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