MSI-target gene-dependent alterations of cell surface glycosylation signatures in MSI colorectal cancer cell lines and primary tumors
Final Report Abstract
Our combined use of a TGFBR2/ACVR2-inducible cell line model system and click-it chemistry/mass spectrometry analysis proved to be very successful in identifying de novo synthesized candidate proteins and sialo-proteins in a MMR-deficient genetic background. It also demonstrated that two major signaling pathways and well-known drivers of MSI tumorigenesis can cause significant proteomic and glycomic alterations. Candidate proteins and / or altered glycan structures newly expressed in our TGFBR2/ACVR2-deficient cell line model system reflect the TGFBR2/ACVR2-deficiency observed in most MMR-deficient colorectal tumors and thus may play a key role in the altered (glyco)biology of these tumors. In terms of clinical relevance, these proteomic/glycomic alterations provide a novel source of potential targets for the design of diagnostic markers and therapeutic strategies for MMR-deficient tumors. Finally, our strategy bears the potential of general applicability because it can easily be adapted to the analysis of any gene of interest and its effect on the cellular de novo proteome and glycome.
Publications
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(2014) De Novo Proteome Analysis of Genetically Modified Tumor Cells By A Click-Chemistry Approach. Mol Cell Proteomics 13:3446-56
Ballikaya S, Lee J, Warnken U, Schnölzer M, Gebert J, Kopitz J
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(2015) Reconstitution of TGFBR2-Mediated Signaling Causes Upregulation of GDF-15 in HCT116 Colorectal Cancer Cells. PloS One, 10(6): e0131506
Lee J, Fricke F, Warnken U, Schnölzer M, Kopitz J, Gebert J
