Fucosyltransferase IV Enhances Expression of MMP-12 Stimulated by EGF via the ERK1/2, p38 and NF-kB Pathways in A431Cells

Abstract

Fucosyltransferase IV (FUT4) has been implicated in cell adhesion, motility, and tumor progression inhuman epidermoid carcinoma A431 cells. We previously reported that it promotes cell proliferation throughthe 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 matrixmetalloproteinase (MMP)-12 induced by EGF in A431 cells. Treatment with EGF resulted in an alteration ofcell morphology and induced an increase in the expression of MMP-12. EGF induced nuclear translocation ofnuclear factor kB (NF-kB) and resulted in phosphorylation of IkBα in a time-dependent manner. In addition,ERK1/2 and p38 MAPK were shown to play a crucial role in mediating EGF-induced NF-kB translocationand phosphorylation of IkBα when treated with the MAPK inhibitors, PD98059 and SB203580, which resultedin increased MMP-12 expression. Importantly, we showed that FUT4 up-regulated EGF-induced MMP-12expression by promoting the phosphorylation of ERK1/2 and p38 MAPK, thereby inducing phosphorylation/degradation of IkBα, NF-kB activation. Base on our data, we propose that FUT4 up-regulates expression ofMMP-12 via a MAPK-NF-kB-dependent mechanism.