Interleukin-5 enhances the migration and invasion of bladder cancer cells via ERK1/2-mediated MMP-9/NF-kappa B/AP-1 pathway: Involvement of the p21WAF1 expression
- Authors
- Lee, Eo-Jin; Lee, Se-Jung; Kim, Sangtae; Cho, Seok-Cheol; Choi, Yung Hyun; Kim, Wun-Jae; Moon, Sung-Kwon
- Issue Date
- Oct-2013
- Publisher
- ELSEVIER SCIENCE INC
- Keywords
- IL-5; IL-5R alpha; p21WAF1; Migration; ERK1/2; MMP-9
- Citation
- CELLULAR SIGNALLING, v.25, no.10, pp 2025 - 2038
- Pages
- 14
- Journal Title
- CELLULAR SIGNALLING
- Volume
- 25
- Number
- 10
- Start Page
- 2025
- End Page
- 2038
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/14236
- DOI
- 10.1016/j.cellsig.2013.06.004
- ISSN
- 0898-6568
1873-3913
- Abstract
- Inflammatory cytokines may be a critical component of epithelial cancer progression. We examined the role of interleukin (IL)-5 in the migration of bladder cancer cells. The expression of IL-5 and its receptor IL-5R alpha was enhanced in patients with muscle invasive bladder cancers (MIBC), and then it was detected in bladder cancer cell lines 5637 and T-24. IL-5 increased migration and MMP-9 expression via activation of transcription factors NF-kappa B and AP-1, and induced activation of ERK1/2 and Jak-Stat signaling in both cells. Treatment with ERK1/2 inhibitor U0126 significantly inhibited induction of migration, MMP-9 expression, and activation of NF-kappa B and AP-1 in IL-5-treated cells. However, none of the Jak inhibitors affected the IL-5-induced migration of bladder cancer cells. Moreover, gene knockdown for IL-5R alpha, using siRNA transfection, suppressed migration, ERK1/2 activation, MMP-9 expression, as well as the binding activation of NF-kappa B and AP-1 in IL-5-treated bladder cancer cells. Similar results were observed in beta c siRNA (si-beta c) transfected cells. Unexpectedly, IL-5 treatment resulted in significant induction of p21WAF1 in both cell lines. The p21WAF1-specific small interfering RNA inhibited IL-5-induced cell migration, ERK activity, MMP-9 expression, and activation of NF-K kappa B and AP-1 in bladder cancer cells. The effects of IL-5-induced cell responses were confirmed by transfection of IL-5 gene, which demonstrated that p21WAF1 participates in the induction of cell migration, leading to an increase in ERK1/2-mediated MMP-9 expression through activation of NF-kappa B and AP-1 in IL-5-treated bladder cancer cells. These unexpected results provide a theoretical basis for the therapeutic targeting of IL-5 in bladder cancer. (C) 2013 Elsevier Inc All rights reserved.
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