Protein-linked glycans play key roles in cell differentiation, cell–cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Thus it can serve as cancer biomarker and treatment target.
What we do
We develop and apply proteomic and glycomic methods to identify altered glycoprotein structures in MSI-H colon cancer. In addition we explore how lectins, in particular galectins, translate the information encoded in the altered glycostructures into biological effects. Moreover, we are pursuing an approach that allows to specifically modify cancer cell glycosylation by drug treatment.
Why we do it
Our research on the glycobiology of MSI-H cancers is part of our activities to develop more clinical interventions in the future. A main pillar is the identification of tumor-specific glycans as potential diagnostic and therapeutic targets. Another focus is on the characterization of the cellular responses evoked upon binding of galectins to tumor cell-associated glycans. Finally drug induced alteration of cell surface glycosylation may provide an entirely new tool to induce a set of neo-glycoantigens that can be targeted by a vaccine.
- 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.
- 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;69(12):962-970
- 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; 67, 218-226.
- 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;24(10):1686-94.
- Lee J, Fricke F, Warnken U, Schnölzer M, Kopitz J, Gebert J. Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells. PLoS One. 2015;10(6):e0131506.
- Ballikaya S, Lee J, Warnken U, Schnoelzer M, Gebert J, Kopitz J. De Novo Proteome Analysis of Genetically Modified Tumor Cells By A Click-Chemistry Approach. Mol Cell Proteomics. 2014 Dec;13(12):3446-56.
- Lee J, Ballikaya S, Schönig K, Ball CR, Glimm H, Kopitz J, Gebert J.bTransforming growth factor beta receptor 2 (TGFBR2) changes sialylation in the microsatellite unstable (MSI) Colorectal cancer cell line HCT116. PLoS One. 2013;8(2):e57074.