Effect of IL-17A on the Migration and Invasion of NPC Cells and Related Mechanisms

Wang, Lixin; Ma, Ruixia; Kang, Zhao-Peng; Zhang, Yupeng; Ding, Hongfa; Guo, Weina; Gao, Qing; Xu, Min

doi:10.1371/journal.pone.0108060

Cited by 19 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 In two human nasopharyngeal cancer cell lines, IL-17 induces expression of MMP2 and MMP9 through activation of p38 kinase and NF-κB pathways, which is accompanied with decreased full-length E-cadherin and increased vimentin levels. 52 It is not clear whether MMP2 and MMP9 expression plays any role in regulating E-cadherin and vimentin levels in that study. 52 Nevertheless, our present study clearly shows that MMP7 cleaves E-cadherin into sE-cadherin in both human prostate cancer cell lines and mouse prostate tumors, resulting in disruption of E-cadherin-β-catenin complex and release of β-catenin that activates the downstream EMT transcription factors.…”

Section: Discussionmentioning

confidence: 75%

“…52 It is not clear whether MMP2 and MMP9 expression plays any role in regulating E-cadherin and vimentin levels in that study. 52 Nevertheless, our present study clearly shows that MMP7 cleaves E-cadherin into sE-cadherin in both human prostate cancer cell lines and mouse prostate tumors, resulting in disruption of E-cadherin-β-catenin complex and release of β-catenin that activates the downstream EMT transcription factors. Loss of membrane-associated E-cadherin has been shown to trigger β-catenin nuclear localization with subsequent c-Myc expression and cellular proliferation in human colon cancer cells.…”

Section: Discussionmentioning

confidence: 75%

See 1 more Smart Citation

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition

et al. 2016

View full text Add to dashboard Cite

Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer, and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL-17’s action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (Mmp7−/− in abbreviation) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/β-catenin complex to up-regulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double knockout mice recapitulated the weak EMT characteristics observed in Mmp7−/− mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B, and PC-3 cell lines, while siRNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single knockout mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17’s function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17-MMP7-EMT axis as potential targets for developing new strategies in the prevention and treatment of prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 75%

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Worth mentioning is the fact that ZEB1, an essential transcription factor, could facilitate metastasis of cancer cells to promote EMT [39], including in cervical cancer [40]. Moreover, SB203580 was also reported to lead to reduced EMT and decreased invasion of NPC-039 and CNE-2Z cell lines [41], highlighting an important point that inhibiting ZEB1-AS1 expression and blocking p38MAPK signaling pathway could significantly suppress the EMT process in cancer cells. Last but not least, the co-existence of Anisomycin and ZEB1-AS1 siRNA could increase EMT formation, as compared with ZEB1-AS1 siRNA alone, which suggested that ZEB1-AS1 siRNA may reduce metastasis and EMT of Hela cells by blocking the p38MAPK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

Gan¹,

Chen²,

Liu³

et al. 2018

Gynecol Obstet Invest

View full text Add to dashboard Cite

Aim: To investigate whether long non-coding RNA (lncRNA) ZEB1 antisense 1 (ZEB1-AS1) affects cell migration and invasion of cervical cancer by regulating epithelial-mesenchymal transition (EMT) via the p38MAPK pathway. Methods: Human cervical cancer cell line Hela was classified into Control, NC siRNA, ZEB1-AS1 siRNA, SB203580 (p38MAPK pathway inhibitor) and ZEB1-AS1 siRNA + Anisomycin (p38MAPK pathway activator) groups. Quantitative real-time polymerase chain reaction was performed for ZEB1-AS1 expression, Western blotting to measure p38MAPK signaling pathway-/EMT-related proteins, and Wound-healing and Transwell assays to evaluate cell migration and invasion respectively. Results: ZEB1-AS1 was upregulated in cancer tissues and related to major clinicopathological features of cervical cancer. Besides, patients with lower-ZEB1-AS1-expression had a higher 5-year survival rate than those patients with higher-ZEB1-AS1-expression. High ZEB1-AS1 expression and advanced Federation of Gynecology and Obstetrics stage were independent risk factors for patients’ prognosis. Both ZEB1-AS1 siRNA and SB203580 effectively reduced p-p38 expression and the migration and invasion of Hela cells, with elevation of E-cadherin and reduction of Vimentin and N-cadherin. However, inhibitory effects of ZEB1-AS1 siRNA on EMT as well as cell migration and invasion of the Hela cell were reversed by Anisomycin. Conclusion: Inhibition of ZEB1-AS1 can block the p38MAPK signaling pathway, ultimately restricting the EMT and suppressing cell migration and invasion of cervical cancer cells.

show abstract

“…Other investigators have reported that IL‐17 induced EMT via Stat3 in lung adenocarcinoma and enhanced lung cancer cell migration through activating NF‐κB by upregulating ZEB1 expression . IL‐17 promotes nasopharyngeal carcinoma cell migration and invasion by regulation of the expression of MMP‐2/‐9 and EMT via the p38‐NF‐κB signaling pathway . Tumor hypoxia with deregulated expression of HIF leads to poor prognosis of patients diagnosed with solid tumors .…”

Section: Discussionmentioning

confidence: 99%

Targeting Th17‐IL‐17 Pathway in Prevention of Micro‐Invasive Prostate Cancer in a Mouse Model

Zhang

Liu

et al. 2017

The Prostate

View full text Add to dashboard Cite

Background Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. Methods The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected i.p. twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected i.v. once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10-week-old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. Results We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. Conclusions These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice.

show abstract

Effect of IL-17A on the Migration and Invasion of NPC Cells and Related Mechanisms

Cited by 19 publications

References 33 publications

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition

Interleukin-17 promotes prostate cancer via MMP7-induced epithelial-to-mesenchymal transition

Long Non-Coding RNA ZEB1-Antisense 1 Affects Cell Migration and Invasion of Cervical Cancer by Regulating Epithelial-Mesenchymal Transition via the p38MAPK Signaling Pathway

Targeting Th17‐IL‐17 Pathway in Prevention of Micro‐Invasive Prostate Cancer in a Mouse Model

Contact Info

Product

Resources

About