title: VHL-dependent regulation of a β-dystroglycan glycoform and glycogene expression in renal cancer.
abstract: Identification of novel biomarkers and targets in renal cell carcinoma (RCC) remains a priority and one cellular compartment that is a rich potential source of such molecules is the plasma membrane. A shotgun proteomic analysis of cell surface proteins enriched by cell surface biotinylation and avidin affinity chromatography was explored using the UMRC2- renal cancer cell line, which lacks von Hippel-Lindau (VHL) tumour suppressor gene function, to determine whether proteins of interest could be detected. Of the 814 proteins identified ~22% were plasma membrane or membrane-associated, including several with known associations with cancer. This included β-dystroglycan, the transmembrane subunit of the DAG1 gene product. VHL-dependent changes in the form of β-dystroglycan were detected in UMRC2-/+VHL transfectants. Deglycosylation experiments showed that this was due to differential sialylation. Analysis of normal kidney cortex and conventional RCC tissues showed that a similar change also occurred in vivo. Investigation of the expression of genes involved in glycosylation in UMRC2-/+VHL cells using a focussed microarray highlighted a number of enzymes involved in sialylation; upregulation of bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) was validated in UMRC2- cells compared with their +VHL counterparts and also found in conventional RCC tissue. These results implicate VHL in the regulation of glycosylation and raise interesting questions regarding the extent and importance of such changes in RCC.
authors: Cancer Research UK Centre, Leeds Institute of Cancer and Pathology, St. James's University Hospital, Leeds LS9 7TF, UK.
authors: Vassilis
authors: V
authors: Aggelis
authors: Rachel A
authors: RA
authors: Craven
authors: Jianhe
authors: J
authors: Peng
authors: Patricia
authors: P
authors: Harnden
authors: Lana
authors: L
authors: Schaffer
authors: Gilberto E
authors: GE
authors: Hernandez
authors: Steven R
authors: SR
authors: Head
authors: Eamonn R
authors: ER
authors: Maher
authors: Robert
authors: R
authors: Tonge
authors: Peter J
authors: PJ
authors: Selby
authors: Rosamonde E
authors: RE
authors: Banks
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002853:Chromatography, Liquid; D049030:Dystroglycans / Q000235:genetics* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D049030:Dystroglycans; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
references: Cancer Sci. 2010 Sep;101(9):2080-6
references: 20626751
references: Cancer Res. 1999 May 1;59(9):2210-6
references: 10232610
references: Mitochondrion. 2006 Dec;6(6):305-14
references: 17113362
references: Br J Cancer. 2004 Mar 22;90(6):1235-43
references: 15026807
references: J Surg Oncol. 2009 Nov 1;100(6):459-65
references: 19598149
references: FEBS J. 2007 Jul;274(13):3233-56
references: 17535296
references: Hum Pathol. 2001 Aug;32(8):791-5
references: 11521221
references: Cancer Biol Ther. 2007 Dec;6(12):1840-6
references: 18087214
references: J Cell Physiol. 2005 Nov;205(2):163-9
references: 15920757
references: Mol Biosyst. 2011 Jul;7(7):2245-51
references: 21584309
references: J Surg Res. 2011 Nov;171(1):120-6
references: 20338590
references: Proteomics. 2003 Oct;3(10):1947-54
references: 14625857
references: Mol Cell Proteomics. 2012 Jul;11(7):M112.017558
references: 22457533
references: Mol Cell Proteomics. 2007 Sep;6(9):1638-55
references: 17533153
references: Oral Oncol. 2008 Dec;44(12):1139-46
references: 18487074
references: Histopathology. 2008 Nov;53(5):561-6
references: 18983465
references: Science. 1993 May 28;260(5112):1317-20
references: 8493574
references: Biochem Biophys Res Commun. 2006 Jun 30;345(2):867-71
references: 16701552
references: Biochem Pharmacol. 2010 Sep 1;80(5):638-46
references: 20382128
references: Prostate. 2011 Aug 1;71(11):1151-7
references: 21656825
references: Biochim Biophys Acta. 2006 Oct;1764(10):1607-17
references: 17030026
references: Histopathology. 2011 Aug;59(2):180-7
references: 21884196
references: Br J Cancer. 2003 Sep 15;89(6):1067-71
references: 12966427
references: Nucleic Acids Res. 2003 Feb 15;31(4):e15
references: 12582260
references: FASEB J. 2012 Feb;26(2):938-46
references: 22049060
references: Trends Genet. 2000 Jun;16(6):276-7
references: 10827456
references: Clin Cancer Res. 2009 Dec 15;15(24):7582-7592
references: 19996202
references: Neoplasia. 2007 Feb;9(2):166-80
references: 17356713
references: Prostate. 2013 Mar;73(4):398-408
references: 22996647
references: J Biol Chem. 2003 Feb 28;278(9):7607-16
references: 12493773
references: Neoplasia. 2012 Jun;14(6):535-46
references: 22806541
references: Am J Pathol. 2003 Mar;162(3):849-60
references: 12598319
references: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12109-14
references: 19587235
references: Eur J Cancer. 2004 Sep;40(14):2143-51
references: 15341990
references: Anticancer Agents Med Chem. 2008 Jan;8(1):2-21
references: 18220502
references: Pathology. 2010 Apr;42(3):248-54
references: 20350218
references: FEBS Lett. 2000 Nov 10;484(3):194-8
references: 11078877
references: Cancer Res. 2002 Jul 1;62(13):3803-11
references: 12097293
references: Am J Pathol. 2006 Feb;168(2):574-84
references: 16436671
references: Clin Proteomics. 2011 Jun 03;8(1):7
references: 21906357
references: Biochem Soc Trans. 2008 Jun;36(Pt 3):472-8
references: 18481984
references: Proteomics. 2009 Apr;9(8):2118-30
references: 19337990
references: Biochemistry. 2003 Jun 17;42(23):7110-23
references: 12795607
references: IUBMB Life. 2009 Dec;61(12):1143-52
references: 19946898
references: Proteomics. 2006 Jul;6(13):3880-93
references: 16739133
references: Hum Mol Genet. 2001 Jul 15;10(15):1563-9
references: 11468274
references: Br J Cancer. 2006 Aug 7;95(3):298-306
references: 16892042
references: Science. 1999 May 21;284(5418):1372-6
references: 10334995
references: FEBS Lett. 2000 Feb 18;468(1):79-83
references: 10683445
references: Mol Cancer Res. 2003 Apr;1(6):453-62
references: 12692265
references: Nat Biotechnol. 1996 Dec;14(13):1675-80
references: 9634850
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: Bioinformatics. 2003 Jan 22;19(2):185-93
references: 12538238
references: Cancer Biol Ther. 2006 Apr;5(4):441-8
references: 16575202
references: Hematol Oncol Clin North Am. 2011 Aug;25(4):667-86
references: 21763962
references: J Biol Chem. 2009 Apr 24;284(17):11279-84
references: 19244252
references: Anal Chem. 2004 Apr 1;76(7):1817-23
references: 15053638
references: J Cell Physiol. 2007 Nov;213(2):528-39
references: 17516554
references: J Cell Sci. 2000 May;113 ( Pt 10):1717-26
references: 10769203