Differential fucosyltransferase IV expression in squamous carcinoma cells is regulated by promoter methylation

Li, Hongyan; Tong, Shaoming; Liu, Jiwei; Han, Li; Yang, Xuesong; Hou, Hanxue; Qiu, Yan; Wang, Xiao Qi

doi:10.2478/s11658-012-0003-x

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…Increased FUT4 expression has been reported in many cancers, such as gastric, colorectal, and lung cancer (18–20). Our previous study showed that high proliferative ability skin cancer A431 cells carried a higher level of FUT4 than low proliferative capability SCC12 cells (21). Moreover, high expression of FUT4 promoted cell proliferation by augmenting the synthesis of LeY (22), while suppressing the expression of FUT4 by RNAi technology reduced the synthesis of LeY and inhibited cell growth (9).…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Shan

Aziz

Tian

et al. 2015

International Journal of Oncology

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Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.

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Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Shan

Aziz

Tian

et al. 2015

International Journal of Oncology

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“…FUT4 expression is increased in various tumor cells (Julien et al, 2011;Padro et al, 2011;Li et al, 2012) and regulated by promoter methylation (Li et al, 2012). In breast cancer cells, FUT4 induced activation of phosphatidylinositol 3 kinase (PI3K)/AKT, and inactivation of glycogen synthase kinase 3 beta (GSK3b) and nuclear translocation of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-lB), resulting in increased Snail and MMP-9 expression and greater cell mobility (Yang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity

Blair

Yuen

et al. 2015

MHR: Basic Science of Reproductive Medicine

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Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P < 0.05). The genes associated with these loci had critical biological roles in cellular development, cellular growth and proliferation, cell signaling, cellular assembly and organization by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P < 0.01 for both CLDN4 and FUT4 mRNA expression; P < 0.001 for CLDN4 and P < 0.01 for FUT4 protein expression), and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by small interfering RNA reduced trophoblast invasion, possibly through the altered matrix metalloproteinase (MMP)-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility.

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“…Of the fucosyltransferases involved in the biosynthesis of Lewis type antigens, the methylation of FUT4 promoter has been reported to be inversely correlated with gene overexpression and tumor invasion [ 84 ]. In breast cancer cells, FUT4 overexpression, due to down-regulation of miR-224-3p, is associated with chemoresistance [ 85 ], while its inhibition by miR-493-5p attenuates invasiveness and tumorigenicity [ 86 ].…”

Section: Epigenetic-regulation Of Cancer Associated Structuresmentioning

confidence: 99%

Epigenetic Bases of Aberrant Glycosylation in Cancer

Dall’Olio

Trinchera

2017

IJMS

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In this review, the sugar portions of glycoproteins, glycolipids, and glycosaminoglycans constitute the glycome, and the genes involved in their biosynthesis, degradation, transport and recognition are referred to as “glycogenes“. The extreme complexity of the glycome requires the regulatory layer to be provided by the epigenetic mechanisms. Almost all types of cancers present glycosylation aberrations, giving rise to phenotypic changes and to the expression of tumor markers. In this review, we discuss how cancer-associated alterations of promoter methylation, histone methylation/acetylation, and miRNAs determine glycomic changes associated with the malignant phenotype. Usually, increased promoter methylation and miRNA expression induce glycogene silencing. However, treatment with demethylating agents sometimes results in silencing, rather than in a reactivation of glycogenes, suggesting the involvement of distant methylation-dependent regulatory elements. From a therapeutic perspective aimed at the normalization of the malignant glycome, it appears that miRNA targeting of cancer-deranged glycogenes can be a more specific and promising approach than the use of drugs, which broad target methylation/acetylation. A very specific type of glycosylation, the addition of GlcNAc to serine or threonine (O-GlcNAc), is not only regulated by epigenetic mechanisms, but is an epigenetic modifier of histones and transcription factors. Thus, glycosylation is both under the control of epigenetic mechanisms and is an integral part of the epigenetic code.

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Differential fucosyltransferase IV expression in squamous carcinoma cells is regulated by promoter methylation

Cited by 6 publications

References 25 publications

Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression

Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity

Epigenetic Bases of Aberrant Glycosylation in Cancer

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