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.

摘要: Protein-linked glycans play key roles in cell differentiation, cell-cell interactions, growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells involved escape from apoptosis, metastasis formation, resistance to therapy. It can serve as cancer biomarker treatment target. To enable comprehensive screening for the impact driving mutations colorectal we present method specific analysis driver-induced glycome changes. The strategy based on combination three technologies, that recombinase-mediated cassette exchange (RMCE), Click-It chemistry mass spectrometry. new exemplified by inactivating TGF-s-receptor type II (TGFBR2) sialic acid incorporation into protein-linked colon line HCT116. Overall, 70 proteins were found show de novo exclusively upon TGFBR2 expression whereas 7 lost sialylation reconstitution. Validation detected candidate glycoproteins demonstrated with surface glycoprotein nectin-3 known be metastasis, invasion prognosis various cancers. Altogether, our approach help systematically puzzle out influence tumor-specific major signaling pathway, suppressor, glycome. facilitates identification glycan-based markers could used diagnostic therapeutic applications. In principle outlined adapted any line, driver mutation several glycan-building blocks.