Fucosyltransferase IV enhances expression of MMP-12 stimulated by EGF via the ERK1/2, p38 and NF-κB pathways in A431 cells

Abstract

Fucosyltransferase IV (FUT4) has been implicated in cell adhesion, motility, and tumor progression in human epidermoid carcinoma A431 cells. We previously reported that it promotes cell proliferation through the ERK/MAPK and PI3K/Akt signaling pathways; however, the molecular mechanisms underlying FUT4- induced cell invasion remain unknown. In this study we determined the effect of FUT4 on expression of matrix metalloproteinase (MMP)-12 induced by EGF in A431 cells. Treatment with EGF resulted in an alteration of cell morphology and induced an increase in the expression of MMP-12. EGF induced nuclear translocation of nuclear factor κB (NF-κB) and resulted in phosphorylation of IκBα in a time-dependent manner. In addition, ERK1/2 and p38 MAPK were shown to play a crucial role in mediating EGF-induced NF-κB translocation and phosphorylation of IκBα when treated with the MAPK inhibitors, PD98059 and SB203580, which resulted in increased MMP-12 expression. Importantly, we showed that FUT4 up-regulated EGF-induced MMP-12 expression by promoting the phosphorylation of ERK1/2 and p38 MAPK, thereby inducing phosphorylation/ degradation of IκBα, NF-κB activation. Base on our data, we propose that FUT4 up-regulates expression of MMP-12 via a MAPK-NF-κB-dependent mechanism.