The Enzymatic Basis for the Conversion of Nonfucosylated to Fucosylated &amp;alpha;-Fetoprotein by Acyclic Retinoid Treatment in Human Hepatoma Cells: Activation of &amp;alpha;1-6 Fucosyltransferase

Noda, Katsuhisa; Miyoshi, Eiji; Kitada, Takanori; Nakahara, Susumu; Gao, Cong; Honke, Koichi; Shiratori, Yoshimune; Moriwaki, Hisataka; Sasaki, Yutaka; Kasahara, Akinori; Hori, Masatsugu; Hayashi, Norio; Taniguchi, Naoyuki

doi:10.1159/000067253

Cited by 18 publications

(11 citation statements)

References 45 publications

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“…As discussed, increased levels of core and outer-arm fucosylation have been observed in the serum of patients with HCC(Block et al, 2005a; Comunale et al, 2006; Comunale et al, 2009a; Goldman et al, 2009; Miyoshi, 1999; Noda et al, 2003; Noda et al, 2002; Ohno, 1992). The exact reason for this change is not fully understood.…”

Section: Fucosylation Is Not Universally Increased In Hcc Tissue As Cmentioning

confidence: 95%

“…However, such staining is present only on a small proportion of HCC tissue examined (20%) and thus it does not appear that these increases are the result of a universal increase in the level of the enzyme. Indeed, there have been numerous attempts to explain why increased levels of fucosylation are associated with HCC, such as increased levels of enzyme (FUT8) and substrate (UDP-L-fucose) however, none of these have provided a simple answer(Ito et al, 2001; Miyoshi, 1999; Moriwaki et al, 2007; Noda et al, 2003; Noda et al, 2002). …”

Section: Fucosylation Is Not Universally Increased In Hcc Tissue As Cmentioning

confidence: 99%

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Glycosylation and Liver Cancer

Mehta

Herrera

Block

2015

Advances in Cancer Research

120

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Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

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Section: Fucosylation Is Not Universally Increased In Hcc Tissue As Cmentioning

confidence: 95%

Section: Fucosylation Is Not Universally Increased In Hcc Tissue As Cmentioning

confidence: 99%

Glycosylation and Liver Cancer

Mehta

Herrera

Block

2015

Advances in Cancer Research

120

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“…Several lectin‐based studies have indicated that fucoproteins are increased in various cancers 15‐17. Abnormally fucosylated serum heptoglobin and α‐fetoprotein (AFP) are used widely as tumor markers of hepatocellular carcinoma 15, 16, 18. Profound fucosylation of the serum microenvironment may be a factor that interrupts adhesion and influences the formation of metastases.…”

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confidence: 99%

Serum fucosylation changes in oral cancer and oral precancerous conditions

Shah

Telang

Raval

et al. 2008

Cancer

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BACKGROUND. The objective of the current study was to investigate the clinical usefulness of serum fucose, fucosylated glycoproteins (fucoproteins), fucosyltransferase (FucT), and α‐L‐fucosidase in oral carcinoma. METHODS. Blood samples were collected from 130 patients with untreated oral cancer (OC), from 75 patients with oral precancerous conditions (OPC), and from 100 healthy controls. Cancer patients were followed after the initiation of anticancer treatments, and 75 follow‐up samples were also collected. Serum levels of fucose and α‐L‐fucosidase were measured spectrophotometrically. Fucoproteins were detected by using lectin‐affinity chromatography. FucT activity was analyzed by using radioassay. RESULTS. Serum levels of fucose and fucoprotein were found to be increased significantly in patients with untreated OC compared with controls, patients with OPC, and complete responders (CR) to treatment; whereas the levels were comparable between untreated patients with OC and nonresponders (NR). A similar trend was observed for serum FucT levels, and changes in enzyme activity correlated well with fucose and fucoprotein alterations. The OPC group had significantly increased fucosylation of serum proteins. Furthermore, serum α‐L‐fucosidase activity was markedly higher in patients with untreated OC and in patients with OPC compared with controls. Using receiver operating characteristic curves, a cutoff for α‐L‐fucosidase was determined at >450.6 U/mL, which showed good sensitivity and specificity in OC and OPC compared with controls. The enzyme activity was declined in the CR group but remained higher in the NR group compared with pretreatment levels. Furthermore, various clinicopathologic characteristics were correlated positively with serum fucosylation changes. CONCLUSIONS. The findings of the current study suggest that serum fucosylation has clinical usefulness in the detection of early changes and for monitoring treatment response in patients with OC. Among the markers studied, serum α‐L‐fucosidase was identified as a useful marker for close monitoring of patients during post–treatment follow‐up. Cancer 2008. © 2008 American Cancer Society.

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“…␣1-6 fucosyltransferase (Fut8) is involved in fucosylation of AFP, and we previously succeeded in the purification and cDNA cloning of Fut8 from porcine brain (2) and a human gastric cancer cell line (3). Although the overexpression of Fut8 in Hep3B cells increased the fucosylation rate of AFP, a high expression of Fut8 was also observed in non-cancerous liver cirrhotic tissues as well as HCC tissues (4). Therefore, other factors could be linked to specific incidences of fucosylated AFP in HCC.…”

mentioning

confidence: 99%

Fucosylation of N-Glycans Regulates the Secretion of Hepatic Glycoproteins into Bile Ducts

Nakagawa

Uozumi

Nakano

et al. 2006

Journal of Biological Chemistry

Self Cite

111

102

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Fucosylated ␣-fetoprotein (AFP) is a highly specific tumor marker for hepatocellular carcinoma (HCC). However, the molecular mechanism by which serum level of fucosylated AFP increases in patients with HCC remains largely unknown. Here, we report that the fucosylation of glycoproteins could be a possible signal for secretion into bile ducts in the liver. We compared oligosaccharide structures on glycoproteins in human bile with those in serum by several types of lectin blot analyses. Enhanced binding of biliary glycoproteins to lectins that recognize a fucose residue was observed over a wide range of molecular weights compared with serum glycoproteins. A structural analysis of oligosaccharides by two-dimensional mapping high performance liquid chromatography and matrix-assisted laser desorption ionization time-of flight mass spectrometry confirmed the increases in the fucosylation of biliary glycoproteins. Purification followed by structural analysis on ␣1-antitrypsin, ␣1-acid glycoprotein and haptoglobin, which are synthesized in the liver, showed higher fucosylation in bile than in serum. To find direct evidence for fucosylation and sorting signal into bile ducts, we used ␣1-6 fucosyltransferase (Fut8)-deficient mice because fucosylation of glycoproteins produced in mouse liver was mainly an ␣1-6 linkage. Interestingly, the levels of ␣1-antitrypsin and ␣1-acid glycoprotein were quite low in bile of Fut8-deficient mice as compared with wild-type mice. An immunohistochemical study showed dramatic changes in the localization of these glycoproteins in the liver of Fut8-deficient mice. Taken together, these results suggest that fucosylation is a possible signal for the secretion of glycoproteins into bile ducts in the liver. A disruption in this system might involve an increase in fucosylated AFP in the serum of patients with HCC.

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The Enzymatic Basis for the Conversion of Nonfucosylated to Fucosylated α-Fetoprotein by Acyclic Retinoid Treatment in Human Hepatoma Cells: Activation of α1-6 Fucosyltransferase

Cited by 18 publications

References 45 publications

Glycosylation and Liver Cancer

Glycosylation and Liver Cancer

Serum fucosylation changes in oral cancer and oral precancerous conditions

Fucosylation of N-Glycans Regulates the Secretion of Hepatic Glycoproteins into Bile Ducts

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