Peritoneal metastasis is the main cause of poor prognoses and high mortality in ovarian cancer patients. Abnormal protein glycosylation modification is associated with cancer malignancy. Elevated α1,3-mannosyltransferase 3 (ALG3), which catalyzes the α1,3-mannosylation of glycoproteins, has been found in some malignant tumors. However, the pathological significance of ALG3 and its regulatory mechanism in ovarian cancer metastasis is unclear. The results showed that the level of ALG3/α1,3-mannosylation was higher in human ovarian cancer tissues compared with normal ovarian tissues, as measured by Lectin chip, Western blot and Lectin blot analyses, as well as ovarian tissue microarray analysis. ALG3 was also correlated with the poor prognosis of ovarian cancer patients, according to survival analysis. The downregulation of ALG3 decreased the proliferation, stemness and peritoneal metastasis of ovarian cancer cells. The increase in urokinase plasminogen activator receptor (uPAR) α1,3-mannosylation catalyzed by ALG3 enhanced urokinase plasminogen activator (uPA)/uPAR activation and the interaction of uPAR with a disintegrin and metalloproteinase 8 (ADAM8), which promoted ovarian cancer peritoneal metastasis via the ADAM8/Ras/ERK pathway. Furthermore, decreased ALG3 suppressed ascites formation and the peritoneal metastasis of ovarian cancer cells in mice. This study highlights ALG3 as a potential diagnostic biomarker and prospective therapeutic target for ovarian cancer.

Preeclampsia (PE) is a pregnancy-specific disorder associated with shallow invasion of the trophoblast cells and insufficient remodeling of the uterine spiral artery. Protein glycosylation plays an important role in trophoblast cell invasion. However, the glycobiological mechanism of PE has not been fully elucidated. In the current study, employing the Lectin array, we found that soybean agglutinin (SBA), which recognizes the terminal N-acetylgalactosamine α1,3-galactose (GalNAc α1,3 Gal) glycotype, was significantly increased in placental trophoblast cells from PE patients compared with third-trimester pregnant controls. Upregulating the expression of the key enzyme α1,3 N-acetylgalactosaminyl transferase (GTA) promoted the biosynthesis of terminal GalNAc α1,3 Gal and inhibited the migration/invasion of HTR8/SVneo trophoblast cells. Moreover, the methylation status of GTA promoter in placental tissues from PE patients was lower than that in the third trimester by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis. Elevated GTA expression in combination with the DNA methylation inhibitor 5-azacytidine (5-AzaC) treatment increased the glycotype biosynthesis and impaired the invasion potential of trophoblast cells, leading to preeclampsia. This study suggests that elevated terminal GalNAc α1,3 Gal biosynthesis and GTA expression may be applied as the new markers for evaluating placental function and the auxiliary diagnosis of preeclampsia.

Background: Aberrant protein O-fucosylation mediated by protein O-fucosyltransferase 1 (POFUT1), has emerged as a hallmark of tumorigenesis that regulates key signaling pathways, including Notch, which is frequently dysregulated in cancers. Protein O-fucosylation, catalyzed by POFUT1, regulates Notch signaling and has been implicated in individual cancers, but its pan-cancer expression patterns, clinical significance, and relationship to tumor immunity remain incompletely characterized. Methodology: We conducted a multi-omics bioinformatics analysis using TCGA and other public datasets to evaluate POFUT1 expression across 33 cancer types (n > 10,000). Differential expressions, tumor stage correlations, and survival outcomes were assessed. Immune cell infiltration was estimated using SangerBox and TIMER algorithms, while promoter methylation patterns were analyzed through UALCAN. Functional enrichment and protein–protein interaction networks were constructed to elucidate functional mechanism. Western blot validation in prostate and ovarian cancer cell lines confirmed our computational analysis. Results: POFUT1 showed significant overexpression in 16 of 33 cancer types (FDR-adjusted p < 0.05), with the highest elevation in BRCA (breast invasive carcinoma; log2FC = 2.31) and LUAD (lung adenocarcinoma; log2FC = 2.1). A high POFUT1 expression correlated with poor overall survival in eight cancer types (HR range: 1.8–3.2, p < 0.01) and disease-free survival in seven cancers. POFUT1 levels positively correlated with myeloid-derived suppressor cells (MDSCs) infiltrating in 15 cancer types, while inversely correlated with natural killer T (NKT) cells presence in 15 cancers (mean R = −0.34, p < 0.05), indicating an association with immunosuppressive microenvironments. Promoter hypomethylation in tumors suggested epigenetic dysregulation as a potential driver of its overexpression. Western blot analysis confirmed POFUT1 protein upregulations in prostate and ovarian cancer cell lines (1.7–2.1-fold. p < 0.01), corroborating transcriptomic findings. Conclusion: This pan-cancer study establishes POFUT1 as a critical oncogenic factor linked to aggressive disease, immune evasion, and poor prognosis. Its consistent overexpression and functional impact highlight its potential as a biomarker and target for anticancer therapy. While these computational findings require experimental validation, POFUT1 emerges as a candidate biomarker warranting functional studies and potential therapeutic targeting.