Decreased Expression of Alpha-L-Fucosidase Gene FUCA1 in Human Colorectal Tumors

Otero-Estévez, Olalla; Martínez‐Fernández, Mónica; Vázquez-Iglesias, Lorena; Cadena, Marı́a Páez de la; Rodrı́guez-Berrocal, Francisco Javier; Martínez-Zorzano, Vicenta S.

doi:10.3390/ijms140816986

Cited by 28 publications

(34 citation statements)

References 38 publications

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“…Although we have restricted our subject to the enzymes of O -glycan biosynthesis, the actions of glycosidases, which are involved in O -glycan degradation, may have an important regulatory role. For example, it is known that α - l -fucosidase (EC 3.2.1.51) is downregulated in certain types of colorectal cancer [ 79 ], from which we infer that an increase in Lewis-type epitopes might be the result of both increased fucosyltransferase activity in Golgi and decreased fucosidase activity in either tissue or plasma. In the future, therefore, this model could be extended to include enzymes involved in the catabolism of O-linked glycoproteins.…”

Section: Discussionmentioning

confidence: 89%

A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts

2016

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O-linked glycosylation is an important post-translational modification of mucin-type protein, changes to which are important biomarkers of cancer. For this study of the enzymes of O-glycosylation, we developed a shorthand notation for representing GalNAc-linked oligosaccharides, a method for their graphical interpretation, and a pattern-matching algorithm that generates networks of enzyme-catalysed reactions. Software for generating glycans from the enzyme activities is presented, and is also available online. The degree distributions of the resulting enzyme-reaction networks were found to be Poisson in nature. Simple graph-theoretic measures were used to characterise the resulting reaction networks. From a study of in-silico single-enzyme knockouts of each of 25 enzymes known to be involved in mucin O-glycan biosynthesis, six of them, β-1,4-galactosyltransferase (β4Gal-T4), four glycosyltransferases and one sulfotransferase, play the dominant role in determining O-glycan heterogeneity. In the absence of β4Gal-T4, all Lewis X, sialyl-Lewis X, Lewis Y and Sda/Cad glycoforms were eliminated, in contrast to knockouts of the N-acetylglucosaminyltransferases, which did not affect the relative abundances of O-glycans expressing these epitopes. A set of 244 experimentally determined mucin-type O-glycans obtained from the literature was used to validate the method, which was able to predict up to 98% of the most common structures obtained from human and engineered CHO cell glycoforms.

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Section: Discussionmentioning

confidence: 89%

A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts

2016

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“…In addition, FUCA1 expression is significantly reduced in cancers of the large intestine, and low FUCA1 expression is related to poorer prognosis in patients with cancer of the large intestine or breast. It has previously been reported that FUCA1 mRNA expression is decreased in colorectal cancers . In addition, it was reported that fucosylation promotes cancer development and malignant progression in breast cancers .…”

Section: Discussionmentioning

confidence: 96%

“…It has previously been reported that FUCA1 mRNA expression is decreased in colorectal cancers. (37) In addition, it was reported that fucosylation promotes cancer development and malignant progression in breast cancers. (38) These reports are in agreement with our results, and suggest that FUCA1 may have tumor-suppressive activity, and could be a therapeutic target in the treatment of cancers in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells

Ezawa¹,

Sawai²,

Kawase

et al. 2016

Cancer Science

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The tumor suppressor p53 functions by inducing the transcription of a collection of target genes. We previously attempted to identify p53 target genes by microarray expression and ChIP‐sequencing analyses. In this study, we describe a novel p53 target gene, FUCA1, which encodes a fucosidase. Although fucosidase, α‐l‐1 (FUCA1) has been reported to be a lysosomal protein, we detected it outside of lysosomes and observed that its activity is highest at physiological pH. As there is a reported association between fucosylation and tumorigenesis, we investigated the potential role of FUCA1 in cancer. We found that overexpression of FUCA1, but not a mutant defective in enzyme activity, suppressed the growth of cancer cells and induced cell death. Furthermore, we showed that FUCA1 reduced fucosylation and activation of epidermal growth factor receptor, and concomitantly suppressed epidermal growth factor signaling pathways. FUCA1 loss‐of‐function mutations are found in several cancers, its expression is reduced in cancers of the large intestine, and low FUCA1 expression is associated with poorer prognosis in several cancers. These results show that protein defucosylation mediated by FUCA1 is involved in tumor suppression.

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“…In addition to anaplastic thyroid cancer, FUCA1 expression is downregulated in aggressive forms of colorectal cancers (26), breast cancers (27), and neuroblastomas (28). It should be noted that a gradual decrease in FUCA1 expression was observed with progression of disease from earlier to advanced stages in colorectal cancer (26). Also in the case of thyroid cancer, as shown previously (25) less aggressive thyroid PTCs expressed higher levels of FUCA1, compared with the more aggressive ATCs, which displayed lower levels of FUCA1 expression.…”

Section: Fuca1 Is Transcriptionally Induced By P53mentioning

confidence: 99%

FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status

Tsuchida

Ikeda

Ιshino

et al. 2017

International Journal of Oncology

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Subsequent to the publication of the above paper, the authors noted that: 1) there was an error on Fig. 4, page 2046, in which the symbols of α-L-fucosidase 1 (FUCA1) and fucosyltransferase 8 (FUT8) had been mistakenly labelled the wrong way around (FUCA1 should have been represented by the blue bars, and FUT8 by the red), and 2) the sentence 'Average levels of FUCA1 mRNA were low in ATCs while expression levels in PTC samples were comparable or slightly higher than those present in normal thyroid tissues (Fig. 4)', page 2046, left column, 4th line from the bottom, was not appropriate to explain the result of Fig. 4. Therefore, this sentence is replaced by: 'FUCA1 RNA expression levels were found to be lower in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary thyroid cancer samples (PTCs) and in normal thyroid tissues (Fig. 4)'.The corrected version of Fig. 4 is shown below, which now accurately shows how FUCA1 RNA expression levels were found to be lower in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary thyroid cancer samples (PTCs) and in normal thyroid tissues. We sincerely apologize for the mistake and the inappropriate explanation in the text, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience these chages have caused. Four ATC samples (T11, T12, T14, T17), 8 PTC samples (T1, T2, T3, T4, T5, T6, T9, T10), and 4 normal thyroid tissues (NT1, NT2, NT3, NT4) are shown.

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Decreased Expression of Alpha-L-Fucosidase Gene FUCA1 in Human Colorectal Tumors

Cited by 28 publications

References 38 publications

A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts

A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts

Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells

FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status

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