Overexpression of α1,6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation-independent manner

Kawamoto, Sayuri; Moriwaki, Kazuo; Nakagawa, Tsutomu; Terao, Mineko; Shinzaki, Shinichiro; Yamane-Ohnuki, Naoko; Satoh, Mitsuo; Mehta, Anand; Block, Timothy M.; Miyoshi, Eiji

doi:10.3892/ijo.2011.1005

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…Kladney et al identified that GP73 expression increased in response to interferon γ and that it was inhibited by tumor necrosis factor α (11). Kawamoto et al demonstrated that α1,6-fucosyltransferase enhanced the expression of GP73 (23). However, the precise mechanism of GP73 elevation in HCC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Hou

Xiao

et al. 2013

Oncology Letters

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Golgi protein 73 (GP73) is a resident Golgi type II transmembrane protein that has been reported to markedly increase in chronic liver disease, particularly in hepatocellular carcinoma (HCC). However, it remains unclear as to whether serum GP73 represents a reliable serum marker for the diagnosis of HCC. The aim of the present study was to evaluate the diagnostic value of serum GP73 in patients with HCC and to determine the diagnostic accuracy of measuring serum GP73 in combination with α-fetoprotein (AFP) and γ-glutamyl transferase isoenzyme II (GGT-II) in HCC. Serum GP73 was detected using a time-resolved fluorescence immunological assay (TRFIA) and enzyme-linked immunosorbent assay (ELISA) in 79 HCC cases, including 16 liver cirrhosis, 30 chronic hepatitis and 28 healthy individuals. The correlation between serum GP73 and tumor size and HCC grading was analyzed and the complementary diagnostic value of serum GP73, AFP and GGT-II was evaluated. TRFIA was established for the detection of serum GP73 and was sensitive and reproducible. The expression levels of serum GP73 were markedly higher in the patients with HCC when compared with those of the individuals with liver cirrhosis and chronic hepatitis or the healthy individuals. According to the receiver operating characteristic (ROC) curve, diagnostic sensitivity and specificity for HCC with a cut-off value of 78.1 ng/l were 73.4 and 79.0%, respectively. However, no correlation was identified among serum GP73 and tumor size or grading, and no correlations were identified among serum GP73, AFP and GGT-II. The diagnostic sensitivities for HCC, as detected by TRFIA of GP73, AFP and GGT-II, were 73.4, 55.6 and 68.4%, respectively, and the specificities were 80.0, 86.7 and 97.1%, respectively. The combined determination of these markers increased the diagnostic sensitivity to 96.3% for HCC. TRFIA functions as a sensitive and replicable assay for the detection of serum GP73. The levels of serum GP73 were significantly higher in the HCC group when compared with the individuals with benign liver diseases. Serum GP73 may serve as a potential independent diagnostic candidate for HCC and the combined determination of serum GP73, AFP and GGT-II may increase the diagnostic efficiency of HCC.

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Section: Discussionmentioning

confidence: 99%

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Hou

Xiao

et al. 2013

Oncology Letters

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“…FUT8 transfers a fucose in the Golgi apparatus and was reported to be localized in the Golgi (19). As described above, FUT8⌬SH3 did not have catalytic activity, which might lead to overall misfolding of FUT8⌬SH3 and its entrapment in the ER.…”

Section: Fut8 Sh3 Domain Influences the Cell-surface Localization Of Fut8mentioning

confidence: 92%

“…FUT8 is considered to be localized in the Golgi, having a typical type II topology (19). However, a previous structural study revealed that the FUT8 luminal domain has a unique C-terminal Src homology 3 (SH3) domain (Fig.…”

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confidence: 99%

The SH3 domain in the fucosyltransferase FUT8 controls FUT8 activity and localization and is essential for core fucosylation

Tomida

Takata

Hirata

et al. 2020

Journal of Biological Chemistry

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Core fucose is an N-glycan structure synthesized by α1,6-fucosyltransferase 8 (FUT8) localized to the Golgi apparatus and critically regulates the functions of various glycoproteins. However, how FUT8 activity is regulated in cells remains largely unclear. At the luminal side and uncommon for Golgi proteins, FUT8 has an Src homology 3 (SH3) domain, which is usually found in cytosolic signal transduction molecules and generally mediates protein-protein interactions in the cytosol. However, the SH3 domain has not been identified in other glycosyltransferases, suggesting that FUT8's functions are selectively regulated by this domain. In this study, using truncated FUT8 constructs, immunofluorescence staining, FACS analysis, cell-surface biotinylation, proteomics, and LC-electrospray ionization MS analyses, we reveal that the SH3 domain is essential for FUT8 activity both in cells and in vitro and identified His-535 in the SH3 domain as the critical residue for enzymatic activity of FUT8. Furthermore, we found that although FUT8 is mainly localized to the Golgi, it also partially localizes to the cell surface in an SH3-dependent manner, indicating that the SH3 domain is also involved in FUT8 trafficking. Finally, we identified ribophorin I (RPN1), a subunit of the oligosaccharyltransferase complex, as an SH3-dependent binding protein of FUT8. RPN1 knockdown decreased both FUT8 activity and core fucose levels, indicating that RPN1 stimulates FUT8 activity. Our findings indicate that the SH3 domain critically controls FUT8 catalytic activity and localization and is required for binding by RPN1, which promotes FUT8 activity and core fucosylation.

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“…The SH3 domain is typical of signal transduction molecules in the cytosol, but is unique to FUT8 compared to other glycosyltransferases (and likely plays are an important role in FUT8’s activity and core fucosylation) [ 44 ]. FUT8 is mainly localized to the Golgi with a type II topology, however, Tomida et al have reported that FUT8 can be partially localized to the cell surface in an SH3-dependent manner [ 44 , 45 ]. Amino acid His535 in the SH3 domain is an essential residue for the enzymatic activity of FUT8, and ribophorin I (RPN1) has been identified as an SH3-dependent binding protein of FUT8, that can stimulate core fucosylation [ 44 ].…”

Section: Alpha-(16)-fucosyltransferase (Fut8)mentioning

confidence: 99%

FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

Bastian

Scott

Elliott

et al. 2021

IJMS

102

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Aberrant glycosylation is a universal feature of cancer cells that can impact all steps in tumour progression from malignant transformation to metastasis and immune evasion. One key change in tumour glycosylation is altered core fucosylation. Core fucosylation is driven by fucosyltransferase 8 (FUT8), which catalyses the addition of α1,6-fucose to the innermost GlcNAc residue of N-glycans. FUT8 is frequently upregulated in cancer, and plays a critical role in immune evasion, antibody-dependent cellular cytotoxicity (ADCC), and the regulation of TGF-β, EGF, α3β1 integrin and E-Cadherin. Here, we summarise the role of FUT8 in various cancers (including lung, liver, colorectal, ovarian, prostate, breast, melanoma, thyroid, and pancreatic), discuss the potential mechanisms involved, and outline opportunities to exploit FUT8 as a critical factor in cancer therapeutics in the future.

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Overexpression of α1,6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in a fucosylation-independent manner

Cited by 8 publications

References 21 publications

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma

The SH3 domain in the fucosyltransferase FUT8 controls FUT8 activity and localization and is essential for core fucosylation

FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

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