Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of breast cancer

Yan, Xiaomei; Lin, Yue; Liu, Shuai; Aziz, Faisal; Qiu, Yan

doi:10.1016/j.biopha.2014.12.048

Cited by 52 publications

(33 citation statements)

References 30 publications

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“…high incidence of sLex in ER-negative breast tumors coincided with high expression of glycosyltransferases FUT3, FUT4 and ST3GAL6 (20). Previous studies have demonstrated a significant high expression of FUT4 in breast cancer tissues and sera in comparison to normal tissues and sera (21) expression patterns in the two cell lines and breast cancer tissues imply its role as an indicator and functional regulator of breast cancer metastasis.…”

Section: Discussionmentioning

confidence: 86%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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Abstract. Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. IntroductionBreast cancer is the most common invasive cancer and the second cause of cancer-related death in women (1,2). Each year more than a half a million new cases of breast cancer are diagnosed in the US and Europe (3), and in China. Breast cancer is a very heterogeneous disease. Some patients are cured by the surgical removal of the primary tumor while other patients suffer from metastasis and progression of the disease, despite adjuvant therapy. Therefore, it is essential to develop effective and safer therapeutic modalities against breast cancer.Glycosylation is one of the important steps of protein post-translational modifications, and ~50% of proteins are glycosylated (4). Protein glycosylation plays a role in a variety of cellular biological functions, such as cell-cell and cell-substrate adhesion, membrane organization, cell immunogenicity and protein targeting (5). Specific changes in the glycosylation patterns of cell surface glycoprotein have been shown to enhance the metastatic potential of tumor cells. Aberrant expression of fucosylated glycans has also been detected in various types of tumors.The fucosyltransferase (FUT) family is a group of fucosylation synthases that catalyze the transfer of L-fucose (Fuc) from an activated GDP-β-L-Fuc to various acceptor molecules such as N-acetyllactosamine. The transfer of Fuc residue from the donor substrate, GDP-Fuc, is catalyzed to the oligosaccharide acceptor in a1, a1, FUT4, FUT5, FUT6, FUT7, FUT9, FUT10 and FUT1...

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Section: Discussionmentioning

confidence: 86%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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“…However, there are some plausible reports that serum level of galactosyltransferase associated with tumor increases in patients with bladder [34] and ovarian cancer [35]. Besides, the expression level of fucosyltransferase IV, which is involved in the altered glycosylation of cancer, has significantly increased in breast cancer tissues and serum [36]. These previously reported findings together with our results might lead a hypothesis that structural changes in therapeutic mAbs could have occurred to cause interindividual variations in the efficacy and adverse effects in human.…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats

Otani¹,

Yonezawa²,

Tsuda³

et al. 2017

PLoS ONE

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Therapeutic monoclonal antibodies (mAbs) have heterogeneities in their structures. Multiple studies have reported that the variety of post-translational modifications could affect the pharmacokinetic profiles or pharmacological potencies of therapeutic mAbs. Taking into the account that the structural modification of mAbs would affect the efficacy, it is worth investigating the structural alteration of therapeutic mAbs in the blood and the relationship between their structures and pharmacological effects. Herein, we have developed the method to isolate rituximab from plasma in which endogenous IgGs interfere the detection of rituximab, and successfully developed the analytical method with a liquid chromatograph time-of-flight mass spectrometer to detect the structure of rituximab in plasma with errors less than 30 parts per millions. Eight types of carbohydrate chains in rituximab were detected by this method. Interestingly, time-dependent changes in carbohydrate chains such as AAF (G2F) and GnGn (G0) were observed in rats, although the amino acids were stable. Additionally, these structural changes were observed via incubation in plasma as in the rat experiment, suggesting that a certain type of enzyme in plasma caused the alterations of the carbohydrate chains. The present analytical methods could clarify the actual pharmacokinetics of therapeutic mAbs, and help to evaluate the interindividual variations in pharmacokinetics and efficacy.

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“…All these are high mannose-type structures. Another 16 Nglycans were upregulated in C8161 cells (peaks 2, 5, 6,9,11,15,16,17,19,21,25,26,30,31,35, and 37; A375P/ C8161 relative intensity ratio of >0.5; Table 2) and are fucosylated or nonfucosylated neutral oligosaccharides. In order to further gauge different fucosylation levels between the two cell lines, N-glycan composition profiling corresponding to fucosylated oligosaccharides was evaluated.…”

Section: Maldi-tof-ms Analysis Of Nglycan Composition Profiling Fromentioning

confidence: 99%

“…Our previous study demonstrated that high metastatic skin cancer A431 cells had a higher level of FUT4 expression than low metastatic SCC12 cells, whose proliferative metastatic ability is much lower . Yan et al reported that FUT4 expression was higher in high metastatic breast cancer cells than in low metastatic cells . However, the effect of FUT4 on the migration and invasion of human melanoma is largely unknown.…”

Section: Introductionmentioning

confidence: 97%

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Role of fucosyltransferase IV in the migration and invasion of human melanoma cells

et al. 2020

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Malignant melanoma is one of the most aggressive human tumor types, mainly due to its high invasion capability, metastatic properties, and the absence of effective treatments. Glycosylation serves a pivotal role in the migration and invasion of melanoma. However, differences in glycosylation between high and low metastatic melanoma cells and how these regulate migration and invasion by altering the expression of fucosyltransferases (FUTs) remain unclear. In the present study, matrix‐assisted laser desorption/ionization‐time‐of‐flight‐mass spectrometry (MALDI‐TOF‐MS) analysis revealed that the composition profiling of fucosylated N‐glycans differed between high metastatic C8161 and low metastatic A375P cells. Further analysis revealed that FUT4 expression was significantly increased in C8161 cells. Melanoma tissue arrays further demonstrated that FUT4 was overexpressed in metastatic samples. Altered FUT4 expression was accompanied by a change in the migration and invasion capacity of the cells. In addition, the migration and invasion potential of melanoma cells were decreased in C8161 and increased in A375P cells upon altering FUT4 expression levels by small interfering RNA or complementary DNA transfection. Furthermore, regulating FUT4 expression markedly modulated the activity of the phosphoinositide‐3‐kinase/Akt (PI3K/Akt) signaling pathway, which affected melanoma cell migration and invasion. In conclusion, FUT4 is a novel biomarker and regulator of the migration and invasion of melanoma cells and may serve as a therapeutic target for melanoma.

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Fucosyltransferase IV (FUT4) as an effective biomarker for the diagnosis of breast cancer

Cited by 52 publications

References 30 publications

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

Time-Dependent Structural Alteration of Rituximab Analyzed by LC/TOF-MS after a Systemic Administration to Rats

Role of fucosyltransferase IV in the migration and invasion of human melanoma cells

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