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

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.

Clinically, MGAT5 upregulation in the CRC TMA correlated negatively with ZO-1 expression, which is indicative of malignancy and a poor prognosis. This study revealed that MGAT5 promotes EMT in CRC via interactions between multiple antenna glycosylation products and ZO-1 ubiquitination/degradation, indicating that MGAT5 could serve as a promising therapeutic target for CRC.

Interestingly, greater OGA expression resulted in both lower overall survival of colon carcinoma patients and lower disease-free survival of rectum carcinoma patients. Therefore, our data indicates that OGA expression correlates with CSC markers and directly impacts the survival of colorectal carcinoma patients.

We identified an association between an abnormal glycoprofile and several clinical risk factors, proposing the N-glycosylation profile as a potential biomarker of tumor progression in the serrated pathway. The N-glycosylation anatomopathological profile analysis could be further used to decide shorter interval follow-up in patients with SPL.

Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity...Consequently, we propose that MGAT5 could serve as a biomarker to predict patients' responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches.

In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.

By such restriction of substrate specificity, we show that the orthogonal enzyme-substrate pair is suitable to bioorthogonally tag glycoproteins. Through X-ray crystallography and molecular dynamics simulations, we establish the structural basis of MGAT5 engineering, informing the design rules for bioorthogonal precision chemical tools.