Glycoscience
In order to survive under stressful conditions, cancer cells alter their metabolism in a way that supports and facilitates fast proliferation and invasion. Here, carbohydrate metabolism plays a particularly important role. Alongside with development of strong glucose dependence, cancer cells show altered protein glycosylation leading to immune suppression and immune evasion, and promoting metastasis. Our group is working on unravelling the glysolyation alterations, investigating changes in carbohydrate composition and developing novel therapeutic strategies targeting these alterations to eliminate cancer cells.
Recent publications
Katzenmaier EM, Stark HJ, Gebert J, Kopitz J. Galectin-12 colocalizes with splicing factor-rich speckles and shuttles between the nucleus and cytoplasm in colon cancer cells. Journal of Molecular Biochemistry (2018) 7, (28-40)
Katzenmaier EM, Kloor M, Gabius HJ, Gebert J, Kopitz J. Analyzing epigenetic control of galectin expression indicates silencing of galectin-12 by promoter methylation in colorectal cancer. IUBMB Life. 2017 Dec;69(12):962-970. PMID: 29098769.
Kopitz J, Xiao Q, Ludwig AK, Romero A, Michalak M, Sherman SE, Zhou X, Dazen C, Vértesy S, Kaltner H, Klein ML, Gabius HJ, Percec V. Reaction of a Programmable Glycan Presentation of Glycodendrimersomes and Cells with Engineered Human Lectins To Show the Sugar Functionality of the Cell Surface. Angew Chem Int Ed Engl. 2017 Nov 13;56(46):14677-14681. PMID: 28940633
Ludwig AK, Michalak M, Shilova N, André S, Kaltner H, Bovin NV, Kopitz J, Gabius HJ.Studying the Structural Significance of Galectin Design by Playing a Modular Puzzle: Homodimer Generation from Human Tandem-Repeat-Type (Heterodimeric) Galectin-8 by Domain Shuffling. Molecules. 2017 Sep 19;22(9). PMID: 28925965
Gebert J, Schnölzer M, Warnken U, Kopitz J. Combining Click Chemistry-Based Proteomics With Dox-Inducible Gene Expression. Methods Enzymol. 2017;585:295-327. PMID: 28109436
Michalak M, Warnken U, André S, Schnölzer M, Gabius HJ, Kopitz J. Detection of Proteome Changes in Human Colon Cancer Induced by Cell Surface Binding of Growth-Inhibitory Human Galectin-4 Using Quantitative SILAC-Based Proteomics. J Proteome Res. 2016 Dec 2;15(12):4412-4422. PMID: 27801591
Ahadova A, Gebert J, von Knebel Doeberitz M, Kopitz J, Kloor M. Dose-dependent effect of 2-deoxy-D-glucose on glycoprotein mannosylation in cancer cells. IUBMB Life. 2015 Mar;67(3):218-26. PMID: 25854316
Kopitz J. Lipid glycosylation: a primer for histochemists and cell biologists. Histochem Cell Biol. 2017 Feb;147(2):175-198. Review. PMID: 27999995
Lee J, Katzenmaier EM, Kopitz J, Gebert J. Reconstitution of TGFBR2 in HCT116 colorectal cancer cells causes increased LFNG expression and enhanced N-acetyl-d-glucosamine incorporation into Notch1. Cell Signal. 2016 Aug;28(8):1105-13. doi: 10.1016/j.cellsig.2016.04.012. Epub 2016 May 5. PMID: 27156840
Plaschke K, Weigand MA, Fricke F, Kopitz J. Neuroinflammation: effect of surgical stress compared to anaesthesia and effect of physostigmine. Neurol Res. 2016 May; 38(5):397-405. PMID: 27095151
Lee J, Warnken U, Schnölzer M, Gebert J, Kopitz J. A new method for detection of tumor driver-dependent changes of protein sialylation in a colon cancer cell line reveals nectin-3 as TGFBR2 target. Protein Sci. 2015 Oct;24(10):1686-94. doi: 10.1002/pro.2741. Epub 2015 Jul 30. PMID: 26177744
Plaschke K, Kopitz J. In vitro streptozotocin model for modeling Alzheimer-like changes: effect on amyloid precursor protein secretases and glycogen synthase kinase-3. J Neural Transm (Vienna). 2015 Apr;122(4):551-7. doi: 10.1007/s00702-014-1319-7. Epub 2014 Oct 5. PMID: 25283498
Katzenmaier EM, André S, Kopitz J, Gabius HJ. Impact of sodium butyrate on the network of adhesion/growth-regulatory galectins in human colon cancer in vitro. Anticancer Res. 2014 Oct;34(10):5429-38. PMID: 25275038
Ballikaya S, Lee J, Warnken U, Schnölzer M, Gebert J, Kopitz J. De Novo proteome analysis of genetically modified tumor cells by a metabolic labeling/azide-alkyne cycloaddition approach. Mol Cell Proteomics. 2014 Dec;13(12):3446-56. Epub 2014 Sep 15. PMID: 25225355
Kopitz J, Vértesy S, André S, Fiedler S, Schnölzer M, Gabius HJ. Human chimera-type galectin-3: defining the critical tail length for high-affinity glycoprotein/cell surface binding and functional competition with galectin-1 in neuroblastoma cell growth regulation. Biochimie. 2014 Sep;104:90-9. doi: 10.1016/j.biochi.2014.05.010. Epub 2014 Jun 6. PMID: 24909114
Plaschke K, Müller AK, Kopitz J. Surgery-induced changes in rat IL-1β and acetylcholine metabolism: role of physostigmine. Clin Exp Pharmacol Physiol. 2014 Sep;41(9):663-70. PMID: 24890001
Aretz S, Krohne TU, Kammerer K, Warnken U, Hotz-Wagenblatt A, Bergmann M, Stanzel BV, Kempf T, Holz FG, Schnölzer M, Kopitz J. In-depth mass spectrometric mapping of the human vitreous proteome. Proteome Sci. 2013 May 20;11(1):22. PMID: 23688336
Kopitz J, Fik Z, André S, Smetana K Jr, Gabius HJ. Single-site mutational engineering and following monoPEGylation of the human lectin galectin-2: effects on ligand binding, functional aspects, and clearance from serum. Mol Pharm. 2013 May 6;10(5):2054-61. PMID: 23581621
Lee J, Ballikaya S, Schönig K, Ball CR, Glimm H, Kopitz J, Gebert J. Transforming growth factor beta receptor 2 (TGFBR2) changes sialylation in the microsatellite unstable (MSI) Colorectal cancer cell line HCT116. PLoS One. 2013;8(2):e57074. PMID: 23468914
Moderately reduced ATP levels promote oxidative stress and debilitate autophagic and phagocytic capacities in human RPE cells. Schütt F, Aretz S, Auffarth GU, Kopitz J. Invest Ophthalmol Vis Sci. 2012 Aug 9;53(9):5354-61. PMID: 22789922
Gebert J, Kloor M, Lee J, Lohr M, André S, Wagner R, Kopitz J, Gabius HJ. Colonic carcinogenesis along different genetic routes: glycophenotyping of tumor cases separated by microsatellite instability/stability. Histochem Cell Biol. 2012 Aug;138(2):339-50. PMID: 22565205
Kopitz J, Ballikaya S, André S, Gabius HJ. Ganglioside GM1/galectin-dependent growth regulation in human neuroblastoma cells: special properties of bivalent galectin-4 and significance of linker length for ligand selection. Neurochem Res. 2012 Jun;37(6):1267-76. doi: 10.1007/s11064-011-0693-x. Epub 2012 Jan 11. PMID: 22234579
Bergmann M, Holz F, Kopitz J. Lysosomal stress and lipid peroxidation products induce VEGF-121 and VEGF-165 expression in ARPE-19 cells. Graefes Arch Clin Exp Ophthalmol. 2011 Oct;249(10):1477-83. Epub 2011 Apr 21. PMID: 21509530
Plaschke K, Fichtenkamm P, Schramm C, Hauth S, Martin E, Verch M, Karck M, Kopitz J. Early postoperative delirium after open-heart cardiac surgery is associated with decreased bispectral EEG and increased cortisol and interleukin-6. Intensive Care Med. 2010 Dec;36(12):2081-9. Epub 2010 Aug 6. PMID: 20689917
Krohne TU, Kaemmerer E, Holz FG, Kopitz J. Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action. Exp Eye Res. 2010 Feb;90(2):261-6. doi: 10.1016/j.exer.2009.10.014. Epub 2009 Nov 4. PMID: 19895809
Kaarniranta K, Salminen A, Eskelinen EL, Kopitz J. Heat shock proteins as gatekeepers of proteolytic pathways-Implications for age-related macular degeneration (AMD). Ageing Res Rev. 2009 Apr;8(2):128-39. Review. PMID: 19274853
Gassler N, Roth W, Funke B, Schneider A, Herzog F, Tischendorf JJ, Grund K, Penzel R, Bravo IG, Mariadason J, Ehemann V, Sykora J, Haas TL, Walczak H, Ganten T, Zentgraf H, Erb P, Alonso A, Autschbach F, Schirmacher P, Knüchel R, Kopitz J. Regulation of enterocyte apoptosis by acyl-CoA synthetase 5 splicing. Gastroenterology. 2007 Aug;133(2):587-98. Epub 2007 Jun 8. PMID: 17681178
André S, Kaltner H, Lensch M, Russwurm R, Siebert HC, Fallsehr C, Tajkhorshid E, Heck AJ, von Knebel Doeberitz M, Gabius HJ, Kopitz J. Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. Int J Cancer. 2005 Mar 10;114(1):46-57. PMID: 15523676
Lukacs Z, Keil A, Peters V, Kohlschütter A, Hoffmann GF, Cantz M, Kopitz J. Towards quality assurance in the determination of lysosomal enzymes: a two-centre study. J Inherit Metab Dis. 2003;26(6):571-81. PMID: 14605503
Kopitz J, André S, von Reitzenstein C, Versluis K, Kaltner H, Pieters RJ, Wasano K, Kuwabara I, Liu FT, Cantz M, Heck AJ, Gabius HJ. Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells. Oncogene. 2003 Sep 18;22(40):6277-88. PMID: 13679866
Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius HJ. Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem. 2001 Sep 21;276(38):35917-23. Epub 2001 Jul 12. PMID: 11451961
Kopitz J, von Reitzenstein C, Burchert M, Cantz M, Gabius HJ. Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. J Biol Chem. 1998 May 1;273(18):11205-11. PMID: 9556610
Our collaborators
Dr. Martina Schnölzer (German Cancer Research Center DKFZ, Functional Proteome Analysis)
Prof. Hans-Joachim Gabius (Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich)
Prof. Peter Krammer, DKFZ, Heidelberg, Germany
Dr. Min Li-Weber, DKFZ, Heidelberg, Germany