MGAT5 (Alpha-1,6-Mannosylglycoprotein 6-Beta-N-Acetylglucosaminyltransferase)

Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistant to YAP1-TEAD-directed therapies.

Collectively, these findings indicate that glycosyltransferases, particularly MGAT5, GCNT1, and ST6GAL1, coordinately shape the GAL1-specific glycome in settings of therapeutic resistance, whereas glycan remodeling by endogenous sialidases does not play a major role. Whether sialidases influence GAL1-dependent functions in other contexts remains to be explored.

Testing their activity on TF-1 cell proliferation, we found that decreases in GM-CSF N -glycan branching significantly suppressed its activity. These findings underscore the importance of glycosylation in modulating the efficacy and safety of GM-CSF-based therapeutics, suggesting that precise glycoengineering may be key to optimizing GM-CSF performance in clinical applications.

Golgi dispersal is associated with increased organelle volume and surface area to accommodate heightened trafficking and processing. These findings position STIM1 and ORP5 as biomarkers of aggressive PCa and show that high-Man enrichment is not due to defective maturation but reflects a glycan pool that cancer cells actively utilize, suggesting that the concept of ER stress response in PCa should be redefined to include Golgi reorganization and altered ER-PM junctions.

Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistant to YAP1-TEAD-directed therapies.

These results imply that branching of O-Man glycans by GnT-IX provides the scaffold for efficient subsequent glycan elongation. Our findings deepen our understanding of the complex biosynthetic pathway of O-Man glycans in the brain.

MGAT5 was significantly upregulated in COAD and correlated with poor prognosis and immune infiltration in COAD. This suggested that MGAT5 may serve as a valuable biomarker for clinical prognosis and a potential target for immunotherapy in COAD.

Our study provides the first molecular roadmap of prostatic PGCA to date, establishing a novel five-gene prognostic signature and revealing fundamental insights into its pathogenesis through divergent evolution from conventional adenocarcinoma. These insights offer new opportunities for precise diagnosis, prognostic stratification, and targeted therapeutic strategies for this lethal prostate cancer variant.

We showed that MGAT5 KO anti-CD19-CAR T cells inhibited the growth of CD19-transduced tumors. Together, these findings show that MGAT5-mediated branched N-glycans regulate CD8+ T-cell function in cancer and provide a strategy to enhance antitumor activity of native and CAR T cells.

ST6Gal-I rs2239611 was a potential genetic biomarker for lung cancer. Areca nut chewing, cigarette smoking, alcohol drinking interacts with glycosyltransferase gene polymorphisms (FUT2 rs1047781 and ST6Gal-I rs2239611), increasing lung cancer risk-a novel finding given the lack of prior studies on this combination.

Proteomic profiling of EVs derived from cells overexpressing MGAT3 and MGAT5 revealed functional changes in EV protein content driven by glycosylation modifications. The study presented a potential multifaced application of melanoma-derived EVs for diagnostic and prognostic purposes.

From the clinical standpoint, we demonstrated that branched N-glycosylation levels detected in inflamed lesions from IBD patients predicted CAC progression with a sensitivity of 83.3% and specificity of 67.9%, when assessed together with age at diagnosis. Overall, we here disclosed a new mechanism underlying CAC development, identifying a potential clinical biomarker plausible to improve the efficacy of cancer surveillance programs through the early identification of high risk IBD patients, for preventive clinical and therapeutic strategies.