Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells

Ramessur, K.T., Greenwell, P., Nash, R. and Dwek, M. 2010. Breast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells. British Journal of Biomedical Science. 67 (4), pp. 189-196.

TitleBreast cancer invasion is mediated by beta-N-acetylglucosaminidase (beta-NAG) and associated with a dysregulation in the secretory pathway of cancer cells
AuthorsRamessur, K.T., Greenwell, P., Nash, R. and Dwek, M.
Abstract

The extracellular matrix is enriched with carbohydrate polymers that mask the protein backbone. This study aims to test the hypothesis that for successful cancer cell invasion the cells must secrete glycosidases to reveal the protein backbone, and then the action of proteases provides the physical space needed for cancer cell movement. Thus, the activity of intracellular and secreted beta-N-acetylglucosaminidase (beta-NAG) was assayed in luminal breast epithelial cells (HB4a) and breast cancer cells (BT474, ZR75-1, MDA-MB-435, MCF7). An increase in the V(max) of beta-NAG was observed in MDA-MB-435 and MCF7 cells. Exoglycosidases are normally located in the lysosomes and function at an acidic pH, but in the cancer cells there was significant enzyme activity at neutral pH. A change in lysosome location and number was observed in the cancer cells, consistent with alterations in the secretory pathway. Finally, applying a cocktail of protease inhibitors resulted in a 20% reduction in invasion of MDA-MB-435 cells through Matrigel after 24 h, and when the cells were treated with protease and beta-NAG inhibitors then cellular invasion was reduced by > 60%. The results suggest combination therapies that inhibit proteases and glycosidases might be a rational way forward for the design of drugs aimed at arresting cellular invasion.

JournalBritish Journal of Biomedical Science
Journal citation67 (4), pp. 189-196
ISSN0967-4845
Year2010
PublisherStep Communications
Web address (URL)http://www.bjbs-online.org/article.asp?id=436
Publication dates
Published2010

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siRNA-mediated inhibition of Na^sup +^ -K^sup +^-2Cl^sup -^ cotransporter (NKCC1) and regulatory volume increase in the chondrocyte cell line C-20/A4
Qusous, A., Geewan, C., Greenwell, P. and Kerrigan, M.J.P. 2011. siRNA-mediated inhibition of Na^sup +^ -K^sup +^-2Cl^sup -^ cotransporter (NKCC1) and regulatory volume increase in the chondrocyte cell line C-20/A4. Journal of Membrane Biology. 243 (1-3), pp. 25-34.

Identification, cloning and characterization of two N-acetylgalactosamine binding lectins from the albumen gland of Helix pomatia
Markiv, A., Peiris, D., Curley, G.P., Odell, M. and Dwek, M. 2011. Identification, cloning and characterization of two N-acetylgalactosamine binding lectins from the albumen gland of Helix pomatia. Journal of Biological Chemistry. 286 (23), pp. 20260-20266.

Cation-π interactions induce kinking of a molecular hinge in the RNA polymerase bridge-helix domain
Heindl, H., Greenwell, P., Weingarten, N., Kiss, T., Terstyanszky, G. and Weinzierl, R.O.J. 2011. Cation-π interactions induce kinking of a molecular hinge in the RNA polymerase bridge-helix domain. Biochemical Society Transactions. 39 (1), pp. 31-35.

Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence
Swann, R., Perkins, A., Dahya, P., Woodside, J., Dutton, S., Robertson, C.E., Velentzis, L.S., Leathem, A. and Dwek, M. 2011. Abstract B76 - An overview of the DietCompLyf study - a multicentre UK study to evaluate the role of diet, lifestyle and complementary medicine use on breast cancer recurrence. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Scientific workflow makespan reduction through cloud augmented desktop grids
Reynolds, C.J., Winter, S., Terstyanszky, G., Kiss, T., Greenwell, P., Acs, S. and Kacsuk, P. 2011. Scientific workflow makespan reduction through cloud augmented desktop grids. in: 2011 IEEE 3rd International Conference on Cloud Computing Technology and Science IEEE . pp. 18-23

Separation and characterization of different isoform populations of PSA in seminal fluid
Lines, A., Clarke, O., Dwek, M., Packer, S. and Edwards, R. 2011. Separation and characterization of different isoform populations of PSA in seminal fluid. American Association for Clinical Chemists Meeting. Atlanta, Georgia 15 - 19 Jul 2011

Development of user-friendly, high throughput screening for ligands and inhibitors of carbohydrate modifying enzymes
Heindl, H., Greenwell, P., Kiss, T., Reynolds, C.J., Farkas, D., Terstyanszky, G. and Winter, S. 2011. Development of user-friendly, high throughput screening for ligands and inhibitors of carbohydrate modifying enzymes. 2nd glyco-bioinformatics Beilstein-Institut symposium. Potsdam, Germany 27th June – 1st July 2011

Abstract LB14 - Lectin microarray profilling of metastatic breast cancers
Fry, S., Afrough, B., Lomax-Browne, H., Timms, J.F., Velentzis, L.S. and Dwek, M. 2011. Abstract LB14 - Lectin microarray profilling of metastatic breast cancers. National Cancer Research Institute (NCRI) Cancer Conference 2011. BT Convention Centre, Liverpool, UK 06 - 09 Nov 2011

Molecular docking simulations on a combined desktop and service grid infrastructure
Kiss, T., Szmetanko, G., Terstyanszky, G., Greenwell, P. and Heindl, H. 2010. Molecular docking simulations on a combined desktop and service grid infrastructure. in: Proceedings: Third AlmereGrid Desktop Experience workshop: desktop grid applications for eScience and eBusiness, 30 March 2010, Almere, The Netherlands EnterTheGrid. pp. 23-27

Parameter sweep workflows for modelling carbohydrate recognition
Kiss, T., Greenwell, P., Heindl, H., Terstyanszky, G. and Weingarten, N. 2010. Parameter sweep workflows for modelling carbohydrate recognition. Journal of Grid Computing. 8 (4), pp. 587-601.

ProSim: development of a user-friendly molecular modelling package
Heindl, H., Kiss, T., Terstyanszky, G., Weingarten, N., Afrough, B. and Greenwell, P. 2010. ProSim: development of a user-friendly molecular modelling package. in: Hicks, M.G. and Kettner, C. (ed.) Proceedings of the International Beilstein Symposium on Glyco-Bioinformatics: Bits ‘n’ Bytes of Sugars, October 4th – 8th, 2009, Potsdam, Germany Beilstein-Institut zur Fo¨rderung der Chemischen Wissenschaften. pp. 61-85

Cytoplasmic hybrid clones (cybrids) for stem cell production: ground-breaking research or a technology too far?
Greenwell, P. 2010. Cytoplasmic hybrid clones (cybrids) for stem cell production: ground-breaking research or a technology too far? Law, Science and Policy. 3, pp. 287-308.

Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions
Dwek, M. 2010. Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions. Discovery-Summit. Majestic Barrière Hotel, Cannes, France 22nd – 24th March 2010

Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions
Dwek, M. 2010. Revealing real-time cell surface interaction analysis: a focus on lectin - cell glycan interactions. Informa Life Sciences 6th Annual Next Generation Protein Therapeutics. Sheraton Brussels Hotel, Belgium 28th – 29th September 2010

GalNAc-recognition by lectins for cancer prognostication
Dwek, M. 2010. GalNAc-recognition by lectins for cancer prognostication. 105th Annual Meeting of the Anatomische Gesellschaft. Hamburg, Germany 29th March 2010

An evaluation of breast cancer cell line sialyltransferase expression levels and assessment of possible correlation with HPA lectin binding profiles
Blaszczak, E., Greenwell, G. and Dwek, M. 2010. An evaluation of breast cancer cell line sialyltransferase expression levels and assessment of possible correlation with HPA lectin binding profiles. Horizons in Molecular Biology: International PhD Student Symposium. Göttingen, Germany 27 - 30 Sep 2010

A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia
Dwek, M., Jenks, A. and Leathem, A. 2010. A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia. Clinica Chimica Acta. 411 (23-24), pp. 1935-1939.

Cancer prognostication using a recombinant form of the lectin from Helix pomatia agglutinin
Dwek, M., Markiv, A. and Odell, M. 2009. Cancer prognostication using a recombinant form of the lectin from Helix pomatia agglutinin. Glycobiology. 19 (11), p. 1318.

UEA-1 enables discrimination between prostate specific antigen from patients with prostate cancer and benign prostatic hyperplasia
Dwek, M., Jenks, A. and Leathem, A. 2009. UEA-1 enables discrimination between prostate specific antigen from patients with prostate cancer and benign prostatic hyperplasia. Glycobiology. 19 (11), p. 1318.

Expression of the c-myc oncogene and the presence of HPV 18: possible surrogate markers for cervical cancer?
Rughooputh, S., Manraj, S., Eddoo, R. and Greenwell, P. 2009. Expression of the c-myc oncogene and the presence of HPV 18: possible surrogate markers for cervical cancer? British Journal of Biomedical Science. 66 (2), pp. 74-78.

ABO reverse grouping: effect of varying concentrations of the enzyme bromelain
Rookard, L.E., Edmondson, O. and Greenwell, P. 2009. ABO reverse grouping: effect of varying concentrations of the enzyme bromelain. British Journal of Biomedical Science. 66 (2), pp. 93-97.

Purification and analysis of DNases of Tritrichomonas foetus: evidence that these enzymes are glycoproteins
Greenwell, P., Younes, M. and Rughooputh, S. 2008. Purification and analysis of DNases of Tritrichomonas foetus: evidence that these enzymes are glycoproteins. International Journal for Parasitology. 38 (7), pp. 749-756.

Proteome analysis of metastatic colorectal cancer cells recognized by the lectin Helix pomatia agglutinin (HPA)
Saint-Guirons, J., Zeqiraj, E., Schumacher, U., Greenwell, P. and Dwek, M. 2007. Proteome analysis of metastatic colorectal cancer cells recognized by the lectin Helix pomatia agglutinin (HPA). Proteomics. 7 (22), pp. 4082-4089.

Colorectal cancer – a sticky problem
Dwek, M. 2007. Colorectal cancer – a sticky problem. Oncology News. 2 (3), pp. 19-21.

Identification and elimination of false-positives in an ELISA-based system for qualitative assessment of glycoconjugate binding using a selection of plant lectins
Afrough, B., Dwek, M. and Greenwell, P. 2007. Identification and elimination of false-positives in an ELISA-based system for qualitative assessment of glycoconjugate binding using a selection of plant lectins. BioTechniques. 43 (4), pp. 458-462.

Chikungunya virus: an emerging problem?
Rughooputh, S. and Greenwell, P. 2007. Chikungunya virus: an emerging problem? Biomedical Scientist.

Predictors of axillary lymph node metastasis in breast cancer: a systematic review
Patani, N.R., Dwek, M. and Douek, M. 2007. Predictors of axillary lymph node metastasis in breast cancer: a systematic review. European Journal of Surgical Oncology. 33 (4), pp. 409-419.

Prevalence of human papillomavirus amongst cervical cancer sufferers amongst slum dwellers in India
Rughooputh, S., Kachaliya, S., Jetly, D. and Greenwell, P. 2007. Prevalence of human papillomavirus amongst cervical cancer sufferers amongst slum dwellers in India. British Journal of Biomedical Science. 64 (1), pp. 28-31.

Cervical cancer and human papillomavirus among slum dwellers in India
Rughooputh, S., Kachaliya, S., Jetly, D. and Greenwell, P. 2007. Cervical cancer and human papillomavirus among slum dwellers in India. British Journal of Biomedical Science. 64 (1), pp. 28-31.

Detection of human papillomavirus from archival tissues in cervical cancer patients in Mauritius
Rughooputh, S., Eddoo, R., Manraj, S., Jeebun, N. and Greenwell, P. 2006. Detection of human papillomavirus from archival tissues in cervical cancer patients in Mauritius. Journal of Clinical Virology. 35 (2), pp. 173-178.

A proteomic approach to identify the integrins α 6 and α V as HPA binding partners in the metastatic colorectal cancer cell line HT29
Saint-Guirons, J., Zeqiraj, E., Greenwell, P. and Dwek, M. 2006. A proteomic approach to identify the integrins α 6 and α V as HPA binding partners in the metastatic colorectal cancer cell line HT29. Molecular and Cellular Proteomics. 5 (10 (supplement)), p. S148.

Association between HPV and C-MYC gene expression in cervical cancer
Rughooputh, S., Eddoo, R., Manraj, S., Jeebun, N. and Greenwell, P. 2006. Association between HPV and C-MYC gene expression in cervical cancer. International Journal of Molecular Medicine. 18 (supplement).

Analysis of glycosidases activity in Chlamydia trachomatis L2 serotype
Greenwell, P., Kakourou, G. and Rughooputh, S. 2006. Analysis of glycosidases activity in Chlamydia trachomatis L2 serotype. Internet Journal of Medical Update. 1 (1).

Vaccination against cervical cancer
Greenwell, P. and Rughooputh, S. 2005. Vaccination against cervical cancer. Biomedical Scientist. 49 (6), p. 441.

Proteomics: more than just biochemistry
Greenwell, P. and Rughooputh, S. 2005. Proteomics: more than just biochemistry. Biomedical Scientist. 49 (6), pp. 459-460.

Confocal microscopy for the identification of glycosylation changes associated with metastatic colorectal cancer
Zeqiraj, E., Saint-Guirons, J., Kerrigan, M.J.P. and Dwek, M. 2005. Confocal microscopy for the identification of glycosylation changes associated with metastatic colorectal cancer. The Molecular Biology of Colorectal Cancer. UBHT Education Centre, Bristol, UK 10 - 11 Mar 2005

Trichomonas vaginalis: paradigm of a successful sexually transmitted organism
Rughooputh, S. and Greenwell, P. 2005. Trichomonas vaginalis: paradigm of a successful sexually transmitted organism. British Journal of Biomedical Science. 62 (4), pp. 193-200.

The metabolic role of methymalonyl CoA mutase in Escherichia coli
Kannan, S.M., Dwek, M., Bucke, C. and Roy, I. 2005. The metabolic role of methymalonyl CoA mutase in Escherichia coli. Proceedings of Viteomics: structure and function of vitamins and cofactors. Cambridge, UK 2005

Application of recombinant phage display antibody system in study of Codakia orbicularis gill proteins
Gourdine, J.P., Greenwell, P. and Smith-Ravin, E.J. 2005. Application of recombinant phage display antibody system in study of Codakia orbicularis gill proteins. Applied Biochemistry and Biotechnology. 125 (1), pp. 41-52.

Structure/function of N-glycans
Dwek, M. 2005. Structure/function of N-glycans. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics. 2nd edition Hoboken, USA Wiley.

Glycoproteomics
Dwek, M. 2005. Glycoproteomics. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics. 2nd edition Hoboken, USA Wiley.

The Unani system of medicine: does it have a scientific basis?
Syeda, A., Rughooputh, S. and Greenwell, P. 2004. The Unani system of medicine: does it have a scientific basis? Biomedical Scientist. 48 (9), pp. 971-972.

Genetically modified food: good news but bad press
Greenwell, P. and Rughooputh, S. 2004. Genetically modified food: good news but bad press. Biomedical Scientist. 48 (8), pp. 845-846.

Bioinformatics: a useful tool for the molecular microbiologist?
Greenwell, P. and Rughooputh, S. 2004. Bioinformatics: a useful tool for the molecular microbiologist? Biomedical Scientist. 48 (5), pp. 494-495.

Detection of human papillomavirus from liquid-based cytology specimens by in-house PCR: a pilot study
Rughooputh, S., Parmar, K. and Greenwell, P. 2004. Detection of human papillomavirus from liquid-based cytology specimens by in-house PCR: a pilot study. British Journal of Biomedical Science. 61 (1), pp. 22-25.

Breast cancer proteomics using 2-dimensional gel electrophoresis
Rawlings, S. and Dwek, M. 2004. Breast cancer proteomics using 2-dimensional gel electrophoresis. in: Brooks, S. and Harris, A. (ed.) Breast cancer research protocols New Jersey, USA Humana Press.

Use of bioinformatics and PCR in the search for ABC transporter homology among various bacteria
Jauhangeer, B.R., Wren, M.W.D., MacDonald, R.A.C., Perry, D. and Greenwell, P. 2004. Use of bioinformatics and PCR in the search for ABC transporter homology among various bacteria. British Journal of Biomedical Science. 61 (4), pp. 182-185.

Harnessing changes in cellular glycosylation in new cancer treatment strategies
Dwek, M. and Brooks, S. 2004. Harnessing changes in cellular glycosylation in new cancer treatment strategies. Current Cancer Drug Targets. 4 (5), pp. 425-442.

Trichomonas vaginalis: an irritating protozoan or an important viral co-factor
Greenwell, P. and Rughooputh, S. 2004. Trichomonas vaginalis: an irritating protozoan or an important viral co-factor. Biomedical Scientist. 48 (1), pp. 40-41.

Human papillomavirus: an overview
Rughooputh, S. and Greenwell, P. 2003. Human papillomavirus: an overview. Biomedical Scientist. 47, pp. 1070-1071.

Isolation of Neisseria gonorrhoeae-specific antibodies from a phage display library
Rughooputh, S. and Greenwell, P. 2003. Isolation of Neisseria gonorrhoeae-specific antibodies from a phage display library. Molecular and Cellular Proteomics. 2 (9), p. 758.

Bioinformatics in the identification of glycosidase genes in the Chlamydia genome
Greenwell, P. and Rughooputh, S. 2003. Bioinformatics in the identification of glycosidase genes in the Chlamydia genome. Molecular and Cellular Proteomics. 2 (9), p. 826.

Phage display antibody against gill proteins of the tropical clam
Gourdine, J.P., Smith-Ravin, E.J. and Greenwell, P. 2003. Phage display antibody against gill proteins of the tropical clam. Molecular and Cellular Proteomics. 2 (9), p. 759.

Incidence and prognostic significance of C-MPL expression in acute myeloid leukemia
Chelvatheebam, S., Langabeer, S., Hills, R., Greenwell, P. and Linch, D. 2003. Incidence and prognostic significance of C-MPL expression in acute myeloid leukemia. Leukemia Research. 27 (9), pp. 839-870.

Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues
Dwek, M. and Alaiya, A.A. 2003. Proteome analysis enables separate clustering of normal breast, benign breast and breast cancer tissues. British Journal of Cancer. 89 (2), pp. 305-307.

Glycoproteomics
Dwek, M. and Mills, P. 2003. Glycoproteomics. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics Chichester, UK Wiley.

Structure/function of N-glycans
Brooks, S. and Dwek, M. 2003. Structure/function of N-glycans. in: Redei, G.P. (ed.) Encyclopedic dictionary of genetics, genomics, and proteomics Chichester, UK Wiley.

Use of proteomic methodology for the characterization of human milk fat globular membrane proteins
Charlwood, J., Hanrahan, S., Tyldesley, R., Langridge, J., Dwek, M. and Camilleri, P. 2002. Use of proteomic methodology for the characterization of human milk fat globular membrane proteins. Analytical Biochemistry. 301 (2), pp. 314-324.

Current perspectives in cancer proteomics
Dwek, M. and Rawlings, S. 2002. Current perspectives in cancer proteomics. Molecular Biotechnology. 22 (2), pp. 139-152.

Functional and molecular glycobiology
Brooks, S., Dwek, M. and Schumacher, U. 2002. Functional and molecular glycobiology. Oxford, UK BIOS Scientific.

Beyond hybridoma technology: production of monoclonal antibodies by phage display
Greenwell, P. and Rughooputh, S. 2001. Beyond hybridoma technology: production of monoclonal antibodies by phage display. Biomedical Scientist. 45, pp. 574-575.

Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer
Dwek, M., Ross, H. and Leathem, A. 2001. Proteome and glycosylation mapping identifies post-translational modifications associated with aggressive breast cancer. Proteomics. 1 (6), pp. 756-63.

Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer
Dwek, M., Ross, H., Streets, A., Brooks, S., Adam, E., Titcomb, A., Woodside, J., Schumacher, U. and Leathem, A. 2001. Helix pomatia agglutinin lectin-binding oligosaccharides of aggressive breast cancer. International Journal of Cancer. 95 (2), pp. 79-85.

Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization
Mobasheri, A., Oukrif, D., Dawodu, S.P., Sinha, M., Greenwell, P., Stewart, D., Djamgoz, M.B.A., Foster, C.S., Martin-Vasallo, P. and Mobasheri, R. 2001. Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization. Histology and Histopathology. 16 (1), pp. 141-154.

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