• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1657-1662
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• 2012

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 kB (NF-${\kappa}B$) and resulted in phosphorylation of $IkB{\alpha}$ in a time-dependent manner. In addition, ERK1/2 and p38 MAPK were shown to play a crucial role in mediating EGF-induced NF-${\kappa}B$ translocation and phosphorylation of $I{\kappa}B{\alpha}$ 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 $I{\kappa}B{\alpha}$, NF-${\kappa}B$ activation. Base on our data, we propose that FUT4 up-regulates expression of MMP-12 via a MAPK-NF-${\kappa}B$-dependent mechanism.

• BMB Reports
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• v.44 no.12
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• pp.772-781
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• 2011

Branched N-glycans are produced by a series of glycosyltransferases including N-acetylglucosaminyltransferases and fucosyltransferases and their corresponding genes. Glycans on specific glycoproteins, which are attached via the action of glycosyltransferases, play key roles in cell adhesion and signaling. Examples of this are adhesion molecules or signaling molecules such as integrin and E-cadherin, as well as membrane receptors such as the EGF and TGF-${\beta}$ receptors. These molecules also play pivotal roles in the underlying mechanism of a variety of disease such as cancer metastasis, diabetes, and chronic obstructive pulmonary disease (COPD). Alterations in the structures of branched N-glycans are also hall marks and are useful for cancer biomarkers and therapeutics against cancer. This mini-review describes some of our recent studies on a functional glycomics approach to the study of branched N-glycans produced by N-acetylglucosaminyltransferases III, IV, V and IX (Vb) (GnT-III, GnT-IV, V and IX (Vb)) and fucosyltransferase 8 (Fut8) and their pathophysiological significance, with emphasis on the importance of a systems glycobiology approach as a future perspective for glycobiology.