IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-κB signal pathway

• Published in: PloS one 2014-09, Vol.9 (9), p.e108502-e108502
• Main Authors: Feng, Minjuan, Wang, Yidong, Chen, Kunlun, Bian, Zhuoqiong, Jinfang Wu, Gao, Qing
• Format: Article
• Language: English
• Subjects: Adult; Biology and Life Sciences; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cervical cancer; Cervix; Cytokines; Female; Gastric cancer; Gelatinase A; Gelatinase B; Gene expression; Gynecology; Hospitals; Humans; Inflammatory diseases; Interleukin-17 - physiology; Invasiveness; Kinases; Liver cancer; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medicine; Medicine and Health Sciences; Metastasis; Middle Aged; Mortality; Neoplasm Invasiveness; Neoplasm Metastasis; NF-kappa B - metabolism; NF-κB protein; Obstetrics; p38 Mitogen-Activated Protein Kinases - metabolism; Pharmacology; Rodents; Stomach cancer; Studies; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; Tumor cell lines; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Western blotting; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108502

IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms. Wound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervical cancer cell migration and invasion by a panel of cervical cancer cell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-κB) signal pathway was detected too. Here, we showed that IL-17A could promote the migration and invasion of cervical cancer cells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervical cancer cells with the pharmacological p38/NF-κB signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A. IL-17A could promote the migration and invasion of cervical cancer cell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-κB signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervical cancer.