Hydrophilic magnetic covalent triazine frameworks for differential N-glycopeptides enrichment in breast cancer plasma membranes

Alterations in plasma membrane glycoproteins (PMGs) have been identified as a hallmark of cancer. The comparison and identification of differential PMGs is significant for finding new markers and understanding pathological processes. However, the research on PMGs is often constrained by the low abundance and the disturbance of abundant endogenous biomolecules during direct analysis. Here, we report a bottom-up strategy to enrich the PMGs of breast cancer cells using hydrophilic magnetic covalent triazine frameworks (CTFs). A total of 972 N-glycopeptides and 1006 N-glycosites belonging to 526 N-glycoproteins were enriched in MCF-10A plasma membrane tryptic digest by magnetic CTFs. And 680 N-glycopeptides and 806 N-glycosites belonging to 443 N-glycoproteins were enriched in SK-BR-3 plasma membrane tryptic digest. Furthermore, comparative analysis was performed based on gene ontology to verify breast cancer biomarkers (SUSD2 and ALCAM) and differential PMGs' function. This strategy which systematically integrates efficient enrichment of differential PMGs and in-depth comparative analysis has great potential for helping illuminate the atlas of breast cancer PMGs and the causes of tumor metastasis.

Automated summary

Alterations in plasma membrane glycoproteins have been identified as a hallmark of cancer. A bottom-up strategy using hydrophilic magnetic covalent triazine frameworks (CTFs) was reported to enrich PMGs of breast cancer cells, leading to the discovery of numerous N-glycopeptides and N-glycosites. Comparative analysis based on gene ontology was performed to verify breast cancer biomarkers and differential PMGs' function, suggesting great potential for illuminating the atlas of breast cancer PMGs and the causes of tumor metastasis.