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

Abstract

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.

MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis

“…Intriguingly, there were no significant changes in total c-Src expression levels or its phosphorylation status by PTP4A2 knockdown (36). Src activation induces Snail and MMP-9 expression (37,38). In this study, miR-1271 inhibited the phosphorylation of c-Src at Tyr416 (Y416), and Snail and MMP-9 expression.…”

Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion

“…FF at 1 Pa activated Src, while FF at 0.25 Pa inactivated Src. Growth factors can activate Src, 41 and we observed that TGFβ1 was upregulated by FFCM at 1 Pa and downregulated by FFCM at 0.25 Pa. Snail expression was also altered by FFCM in a shear stress intensitydependent manner.…”

CoCl2, a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway

“…FAK localizes to sites of transmembrane integrin receptor clustering, and facilitates intracellular signaling events and cell migration (Sieg et al, ; Thakur et al, ). JNK and FAK also signal via CXCR4 and MMP family to facilitate intracellular signaling and cell migration (Liao et al, ; Mon et al, ). We found that hypoxia enhanced JNK and FAK phosphorylation, and STAT3 inhibition suppressed JNK and FAK phosphorylation.…”