ArticleThe Journal of biological chemistry2013
Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-κB) activation by inducing the up-regulation of p21(WAF1) protein expression.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 111 citations in OpenAlex.
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- Rational Identification of Ritonavir as IL-20 Receptor A Ligand Endowed with Antiproliferative Properties in Breast Cancer Cells.International journal of molecular sciences · 2025Article
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- Identification and validation of prognostic signature genes of bladder cancer by integrating methylation and transcriptomic analysis.Scientific reports · 2024Article
- Understanding bladder cancer risk: Mendelian randomization analysis of immune cell and inflammatory factor influence.Frontiers in immunology · 2024Article
- A robust immune-related gene pairs signature for predicting the overall survival of esophageal cancer.BMC genomics · 2023Article
- Head and Neck Cancer Immunotherapy: Molecular Biological Aspects of Preclinical and Clinical Research.Cancers · 2023Review
- A comprehensive review on RNA interference-mediated targeting of interleukins and its potential therapeutic implications in colon cancer.3 Biotech · 2023Review
- HSPA6 and its role in cancers and other diseases.Molecular biology reports · 2022Review
- Comprehensive landscape of the ST3GAL family reveals the significance of ST3GAL6-AS1/ST3GAL6 axis on EGFR signaling in lung adenocarcinoma cell invasion.Frontiers in cell and developmental biology · 2022Article
- Induction ofScience signaling · 2021Article
- MicroRNA 452 regulates IL20RA-mediated JAK1/STAT3 pathway in inflammatory colitis and colorectal cancer.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
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- IL-19 induced by IL-13/IL-17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP-9 expression via ERK/NF-κB signaling pathway.Clinical and translational allergy · 2021Article
- A Novel Cyclic Pentadepsipeptide,Cancers · 2021Article
- IL-20R Activation via rIL-19 Enhances Hematoma Resolution through the IL-20R1/ERK/Nrf2 Pathway in an Experimental GMH Rat Pup Model.Oxidative medicine and cellular longevity · 2021Article
- In Vitro and In Vivo Antitumor Efficacy ofNutrients · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle-invasive bladder cancer patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38 MAPK, and JAK-STAT signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced migration and invasion. Moreover, siRNA knockdown of IL-20R1 suppressed migration, invasion, ERK1/2 activation, and NF-κB-mediated MMP-9 expression induced by IL-20. Unexpectedly, the cell cycle inhibitor p21(WAF1) was induced by IL-20 treatment without altering cell cycle progression. Blockade of p21(WAF1) function by siRNA reversed migration, invasion, activation of ERK signaling, MMP-9 expression, and activation of NF-κB in IL-20-treated cells. In addition, IL-20 induced the activation of IκB kinase, the degradation and phosphorylation of IκBα, and NF-κB p65 nuclear translocation, which was regulated by ERK1/2. IL-20 stimulated the recruitment of p65 to the MMP-9 promoter region. Finally, the IL-20-induced migration and invasion of cells was confirmed by IL-20 gene transfection and by addition of anti-IL-20 antibody. This is the first report that p21(WAF1) is involved in ERK1/2-mediated MMP-9 expression via increased binding activity of NF-κB, which resulted in the induction of migration in IL-20/IL-20R1 dyad-induced bladder cancer cells. These unexpected results might provide a critical new target for the treatment of bladder cancer.
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