p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-kappa B binding in the IL-7-induced migration and invasion of 5637 cells
- Authors
- Park, Sung Lyea; Lee, Eo-Jin; Kim, Wun-Jae; Moon, Sung-Kwon
- Issue Date
- Apr-2014
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- IL-7; bladder cancer cells; migration; invasion; p27KIP1
- Citation
- INTERNATIONAL JOURNAL OF ONCOLOGY, v.44, no.4, pp 1349 - 1356
- Pages
- 8
- Journal Title
- INTERNATIONAL JOURNAL OF ONCOLOGY
- Volume
- 44
- Number
- 4
- Start Page
- 1349
- End Page
- 1356
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/12368
- DOI
- 10.3892/ijo.2014.2290
- ISSN
- 1019-6439
1791-2423
- Abstract
- Interleukin-7 (IL-7) plays a pivotal role in the development and survival of lymphocytes, but its role in cancer cell responses remains unexplained. In this study, IL-7 treatment resulted in a significant induction in the wound-healing migration and Matrigel invasion of the 5637 bladder cancer cells, but it did not result in cell proliferation. In addition, IL-7 treatment strongly induced MMP-9 expression, and increased the binding activation of NF-B and AP-1 motifs, the important transcription factors that regulate MMP-9 expression. Moreover, the treatment of 5637 cells with IL-7 stimulated the phosphorylation of ERK1/2. U0126, an ERK1/2-specific inhibitor, blocked IL-7-induced cell migration and invasion, and also suppressed the expression of MMP-9 in the presence of IL-7. Inhibition of the ERK1/2 function consistently reversed the binding activity of NF-B without altering AP-1 activation in IL-7-stimulated cells. Among the cell cycle regulators examined, only the expression of the cell cycle inhibitor p27KIP1 was induced by IL-7. Moreover, the inhibition of p27KIP1 by small interfering RNA (siRNA) abolished the migration, invasion and phosphorylation of ERK1/2, the expression of MMP-9, and the binding activity of the NF-B motif in IL-7-stimulated 5637 cells. These results demonstrated that the cell cycle inhibitor p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via activation of the NF-B binding motif, which leads to the migration and invasion of bladder cancer cells induced by IL-7. These novel results could help explain the migration and invasion of bladder tumor cells.
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