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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Cancer+Res 2015 ; 5 (3): 1169-79 Nephropedia Template TP
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Interleukin-17-induced EMT promotes lung cancer cell migration and invasion via NF-?B/ZEB1 signal pathway #MMPMID26045995
Gu K; Li MM; Shen J; Liu F; Cao JY; Jin S; Yu Y
Am J Cancer Res 2015[]; 5 (3): 1169-79 PMID26045995show ga
Inflammatory cytokine interleukin-17 (IL-17) has been associated with the risk of progressive cancers including lung cancer. However, it remains unclear how IL-17 may contribute to the invasion and development of these inflammation-associated malignancies. Here we aimed to investigate the role of IL-17 in lung cancer cell development. Epithelial-mesenchymal transition (EMT) has been recently proposed as a developmental process which plays an important role in cancer progression and metastases. Here we show that IL-17 might promote EMT in lung cancer cells by inducing the transcriptional repressor ZEB1. Exposure to IL-17 upregulated the signature EMT phenotypic markers vimentin and E-cadherin in lung cancer cells, and compared with controls, increased cell migration was observed in IL-17-treated lung cancer cells. ZEB1 mRNA and protein expression was induced by IL-17, and IL-17 stimulated nuclear localization of phosphorylated ZEB1. Conversely, suppressing ZEB1 expression by ZEB1 siRNA abrogated IL-17-stimulated vimentin expression and cell migration. Moreover, the phosphorylation of I?B? was required for IL-17-induced expression of ZEB1, suggesting the involvement of canonical NF-?B signaling. To check this hypothesis, we used IKK inhibitor BAY 11-7028 to block NF-?B activity. We found that BAY 11-7028 abrogated IL-17-induced ZEB1 expression, cell migration, and EMT, thus confirming that NF-?B is required for IL-17 to induce these aggressive phenotypes in lung cancer cells. Taken together, our data support the idea that IL-17-induced EMT promotes lung cancer cell migration and invasion via NF-?B-mediated upregulation of ZEB1. This study reveals a new signaling axis through which the tumor microenvironment causes ZEB1 expression to promote cancer metastasis. We suggest that targeting IL-17-induced ZEB1 expression may offer an effective therapeutic strategy for lung cancer treatment.