Interleukin-1β activates focal adhesion kinase and Src to induce matrix metalloproteinase-9 production and invasion of MCF-7 breast cancer cells.

Abstract

Interleukin-1β (IL-1b) is a pleiotropic cytokine that is important in tumor progression and invasion. Matrix metalloproteinase-9 (MMP-9), which is a secreted matrix-degrading enzyme, is one of the key regulators of tumor invasion and metastasis. The current report indicated that IL-1b promotes MMP-9 production and cell invasion in non-metastatic MCF-7 breast cancer cells. IL-1b activated focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase Src (Src). Moreover, inhibiting the Src/FAK pathway reduced the IL-1b-induced production of MMP-9 and cell invasion. To investigate the functional role of FAK in MMP-9 production cell lines expressing mutant FAK in FAK knock-out mouse fibroblasts were generated. In wild-type FAK-expressing cells, MMP-9 production was induced by IL-1b stimulation. By contrast, IL-1b-induced MMP-9 production was abrogated in FAK knock-out, FAK Y397F, FAK Y925F, and kinase dead mutant-expressing cells. Therefore the results of the current study indicate that FAK and Src kinases are activated by IL-1b and play a critical role in MMP-9 production and tumor cell invasion.