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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Identification of α(1,6)fucosylated proteins differentially expressed in human colorectal cancer

Authors: Laura Muinelo-Romay, Susana Villar-Portela, Elisa Cuevas, Emilio Gil-Martín, Almudena Fernández-Briera

Published in: BMC Cancer | Issue 1/2011

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Summary

Background

A universal hallmark of cancer cells is the change in their glycosylation phenotype. One of the most frequent alterations in the normal glycosylation pattern observed during carcinogenesis is the enhancement of α(1,6)linked fucose residues of glycoproteins, due to the up-regulation of the α(1,6)fucosyltransferase activity. Our previous results demonstrated the specific alteration of this enzyme activity and expression in colorectal cancer, suggesting its implication in tumour development and progression.

Methods

In the current work we combined a LCA-affinity chromatography with SDS-PAGE and mass spectrometry in order to identify α(1,6)fucosylated proteins differentially expressed in colorectal cancer. This strategy allowed the identification of a group of α(1,6)fucosylated proteins candidates to be involved in CRC malignancy.

Results

The majority of the identified proteins take part in cell signaling and interaction processes as well as in modulation of the immunological response. Likewise, we confirmed the increased expression of GRP94 in colorectal cancer tissue and the significant down-regulation of the IgGFcBP expression in tumour cells.

Conclusion

All these results validate the importance of core-fucosylated proteins profile analysis to understand the mechanisms which promote cancer onset and progression and to discover new tumour markers or therapeutic targets.
Appendix
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Literature
1.
Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics, 1998. CA Cancer J Clin. 1998, 48 (1): 6-29. 10.3322/canjclin.48.1.6.CrossRefPubMed
2.
Varki A: Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993, 3 (2): 97-130. 10.1093/glycob/3.2.97.CrossRefPubMed
3.
Hakomori S: Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res. 1989, 52: 257-331.CrossRefPubMed
4.
Campion B, Leger D, Wieruszeski JM, Montreuil J, Spik G: Presence of fucosylated triantennary, tetraantennary and pentaantennary glycans in transferrin synthesized by the human hepatocarcinoma cell line Hep G2. Eur J Biochem. 1989, 184 (2): 405-413. 10.1111/j.1432-1033.1989.tb15032.x.CrossRefPubMed
5.
Uozumi N, Teshima T, Yamamoto T, Nishikawa A, Gao YE, Miyoshi E, Gao CX, Noda K, Islam KN, Ihara Y, et al: A fluorescent assay method for GDP-L-Fuc:N-acetyl-beta-D-glucosaminide alpha 1-6fucosyltransferase activity, involving high performance liquid chromatography. J Biochem. 1996, 120 (2): 385-392.CrossRefPubMed
6.
Wang X, Fukuda T, Li W, Gao CX, Kondo A, Matsumoto A, Miyoshi E, Taniguchi N, Gu J: Requirement of Fut8 for the expression of vascular endothelial growth factor receptor-2: a new mechanism for the emphysema-like changes observed in Fut8-deficient mice. J Biochem. 2009, 145 (5): 643-651. 10.1093/jb/mvp022.CrossRefPubMed
7.
Wang X, Gu J, Ihara H, Miyoshi E, Honke K, Taniguchi N: Core fucosylation regulates epidermal growth factor receptor-mediated intracellular signaling. J Biol Chem. 2006, 281 (5): 2572-2577.CrossRefPubMed
8.
Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, Mizuno-Horikawa Y, Nakano M, Asahi M, Takahashi M, et al: Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci USA. 2005, 102 (44): 15791-15796. 10.1073/pnas.0507375102.CrossRefPubMedPubMedCentral
9.
Zhao Y, Itoh S, Wang X, Isaji T, Miyoshi E, Kariya Y, Miyazaki K, Kawasaki N, Taniguchi N, Gu J: Deletion of core fucosylation on alpha3beta1 integrin down-regulates its functions. J Biol Chem. 2006, 281 (50): 38343-38350. 10.1074/jbc.M608764200.CrossRefPubMed
10.
Geng F, Shi BZ, Yuan YF, Wu XZ: The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications. Cell Res. 2004, 14 (5): 423-433. 10.1038/sj.cr.7290243.CrossRefPubMed
11.
Osumi D, Takahashi M, Miyoshi E, Yokoe S, Lee SH, Noda K, Nakamori S, Gu J, Ikeda Y, Kuroki Y, et al: Core fucosylation of E-cadherin enhances cell-cell adhesion in human colon carcinoma WiDr cells. Cancer Sci. 2009, 100 (5): 888-895. 10.1111/j.1349-7006.2009.01125.x.CrossRefPubMed
12.
Yamashiki N, Seki T, Wakabayashi M, Nakagawa T, Imamura M, Tamai T, Nishimura A, Inoue K, Okamura A, Arita S, et al: Usefulness of Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma. Oncol Rep. 1999, 6 (6): 1229-1232.PubMed
13.
Comunale MA, Lowman M, Long RE, Krakover J, Philip R, Seeholzer S, Evans AA, Hann HW, Block TM, Mehta AS: Proteomic analysis of serum associated fucosylated glycoproteins in the development of primary hepatocellular carcinoma. J Proteome Res. 2006, 5 (2): 308-315. 10.1021/pr050328x.CrossRefPubMed
14.
Ang IL, Poon TC, Lai PB, Chan AT, Ngai SM, Hui AY, Johnson PJ, Sung JJ: Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: a glycoproteomic approach. J Proteome Res. 2006, 5 (10): 2691-2700. 10.1021/pr060109r.CrossRefPubMed
15.
Barrabes S, Pages-Pons L, Radcliffe CM, Tabares G, Fort E, Royle L, Harvey DJ, Moenner M, Dwek RA, Rudd PM, et al: Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and reveals an increase in core fucosylation in pancreatic cancer. Glycobiology. 2007, 17 (4): 388-400. 10.1093/glycob/cwm002.CrossRefPubMed
16.
Okuyama N, Ide Y, Nakano M, Nakagawa T, Yamanaka K, Moriwaki K, Murata K, Ohigashi H, Yokoyama S, Eguchi H, et al: Fucosylated haptoglobin is a novel marker for pancreatic cancer: a detailed analysis of the oligosaccharide structure and a possible mechanism for fucosylation. Int J Cancer. 2006, 118 (11): 2803-2808. 10.1002/ijc.21728.CrossRefPubMed
17.
Mechref Y, Madera M, Novotny MV: Glycoprotein enrichment through lectin affinity techniques. Methods Mol Biol. 2008, 424: 373-396. 10.1007/978-1-60327-064-9_29.CrossRefPubMed
18.
Toyoshima S, Osawa T, Tonomura A: Some properties of purified phytohemagglutinin from Lens culinaris seeds. Biochim Biophys Acta. 1970, 221 (3): 514-521.CrossRefPubMed
19.
Kochibe N, Furukawa K: Purification and properties of a novel fucose-specific hemagglutinin of Aleuria aurantia. Biochemistry. 1980, 19 (13): 2841-2846. 10.1021/bi00554a004.CrossRefPubMed
20.
Comunale MA, Wang M, Hafner J, Krakover J, Rodemich L, Kopenhaver B, Long RE, Junaidi O, Bisceglie AM, Block TM, et al: Identification and development of fucosylated glycoproteins as biomarkers of primary hepatocellular carcinoma. J Proteome Res. 2009, 8 (2): 595-602. 10.1021/pr800752c.CrossRefPubMedPubMedCentral
21.
Dai Z, Fan J, Liu Y, Zhou J, Bai D, Tan C, Guo K, Zhang Y, Zhao Y, Yang P: Identification and analysis of alpha1,6-fucosylated proteins in human normal liver tissues by a target glycoproteomic approach. Electrophoresis. 2007, 28 (23): 4382-4391. 10.1002/elps.200700233.CrossRefPubMed
22.
Muinelo-Romay L, Vazquez-Martin C, Villar-Portela S, Cuevas E, Gil-Martin E, Fernandez-Briera A: Expression and enzyme activity of alpha(1,6)fucosyltransferase in human colorectal cancer. Int J Cancer. 2008, 123 (3): 641-646. 10.1002/ijc.23521.CrossRefPubMed
23.
Muinelo-Romay L, Cuevas E, Gil-Martín E, Fernández-Briera A: α(1,6)Fucosyltransferase Expression Is an Independent Prognostic Factor for Disease-Free Survival in Colorectal Carcinoma. Human Pathology. 2011
24.
Hammarstrom S: The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999, 9 (2): 67-81. 10.1006/scbi.1998.0119.CrossRefPubMed
25.
Tomlinson IP, Whyman A, Barrett JA, Kremer JK: Tumour marker CA15-3: possible uses in the routine management of breast cancer. Eur J Cancer. 1995, 31A (6): 899-902.CrossRefPubMed
26.
Hutchinson WL, Du MQ, Johnson PJ, Williams R: Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. Hepatology. 1991, 13 (4): 683-688. 10.1002/hep.1840130412.CrossRefPubMed
27.
Miyoshi E, Noda K, Ko JH, Ekuni A, Kitada T, Uozumi N, Ikeda Y, Matsuura N, Sasaki Y, Hayashi N, et al: Overexpression of alpha1-6 fucosyltransferase in hepatoma cells suppresses intrahepatic metastasis after splenic injection in athymic mice. Cancer Res. 1999, 59 (9): 2237-2243.PubMed
28.
Ito Y, Miyauchi A, Yoshida H, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, et al: Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer Lett. 2003, 200 (2): 167-172. 10.1016/S0304-3835(03)00383-5.CrossRefPubMed
29.
Takahashi T, Ikeda Y, Miyoshi E, Yaginuma Y, Ishikawa M, Taniguchi N: alpha1, 6fucosyltransferase is highly and specifically expressed in human ovarian serous adenocarcinomas. Int J Cancer. 2000, 88 (6): 914-919. 10.1002/1097-0215(20001215)88:6<914::AID-IJC12>3.0.CO;2-1.CrossRefPubMed
30.
Li Z, Srivastava PK: Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation. EMBO J. 1993, 12 (8): 3143-3151.PubMedPubMedCentral
31.
Harada N, Iijima S, Kobayashi K, Yoshida T, Brown WR, Hibi T, Oshima A, Morikawa M: Human IgGFc binding protein (FcgammaBP) in colonic epithelial cells exhibits mucin-like structure. J Biol Chem. 1997, 272 (24): 15232-15241. 10.1074/jbc.272.24.15232.CrossRefPubMed
32.
Nomura H, Uzawa K, Yamano Y, Fushimi K, Ishigami T, Kato Y, Saito K, Nakashima D, Higo M, Kouzu Y, et al: Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis. Br J Cancer. 2007, 97 (6): 792-801. 10.1038/sj.bjc.6603948.CrossRefPubMedPubMedCentral
33.
Heike M, Frenzel C, Meier D, Galle PR: Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer. Int J Cancer. 2000, 86 (4): 489-493. 10.1002/(SICI)1097-0215(20000515)86:4<489::AID-IJC7>3.0.CO;2-D.CrossRefPubMed
34.
Wang X, Wang Q, Guo L, Ying X, Zhao Y: Immunolocalisation of heat shock protein 72 and glycoprotein 96 in colonic adenocarcinoma. Acta Histochem. 2008, 110 (2): 117-123. 10.1016/j.acthis.2007.10.013.CrossRefPubMed
35.
Kaetzel CS: The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol Rev. 2005, 206: 83-99. 10.1111/j.0105-2896.2005.00278.x.CrossRefPubMed
36.
Jia W, Lu Z, Fu Y, Wang HP, Wang LH, Chi H, Yuan ZF, Zheng ZB, Song LN, Han HH, et al: A strategy for precise and large scale identification of core fucosylated glycoproteins. Mol Cell Proteomics. 2009, 8 (5): 913-923. 10.1074/mcp.M800504-MCP200.CrossRefPubMedPubMedCentral
37.
Chang Y, Lee TC, Li JC, Lai TL, Chua HH, Chen CL, Doong SL, Chou CK, Sheen TS, Tsai CH: Differential expression of osteoblast-specific factor 2 and polymeric immunoglobulin receptor genes in nasopharyngeal carcinoma. Head Neck. 2005, 27 (10): 873-882. 10.1002/hed.20253.CrossRefPubMed
38.
Traicoff JL, De Marchis L, Ginsburg BL, Zamora RE, Khattar NH, Blanch VJ, Plummer S, Bargo SA, Templeton DJ, Casey G, et al: Characterization of the human polymeric immunoglobulin receptor (PIGR) 3'UTR and differential expression of PIGR mRNA during colon tumorigenesis. J Biomed Sci. 2003, 10 (6 Pt 2): 792-804.PubMed
39.
Johansson ME, Thomsson KA, Hansson GC: Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein. J Proteome Res. 2009, 8 (7): 3549-3557. 10.1021/pr9002504.CrossRefPubMed
40.
Lee S, Bang S, Song K, Lee I: Differential expression in normal-adenoma-carcinoma sequence suggests complex molecular carcinogenesis in colon. Oncol Rep. 2006, 16 (4): 747-754.PubMed
41.
42.
Kobayashi K, Yagasaki M, Harada N, Chichibu K, Hibi T, Yoshida T, Brown WR, Morikawa M: Detection of Fcgamma binding protein antigen in human sera and its relation with autoimmune diseases. Immunol Lett. 2001, 79 (3): 229-235. 10.1016/S0165-2478(01)00288-7.CrossRefPubMed
Metadata
Title
Identification of α(1,6)fucosylated proteins differentially expressed in human colorectal cancer
Authors
Laura Muinelo-Romay
Susana Villar-Portela
Elisa Cuevas
Emilio Gil-Martín
Almudena Fernández-Briera
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-508

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