GALNT1, a key enzyme mediating O-GalNAc glycosylation, has not been fully characterized in the tumor microenvironment. This study aimed to investigate its expression pattern, molecular mechanisms, and clinical relevance in breast cancer. Public datasets (TCGA, GEO, CPTAC) and single-cell transcriptomic data were integrated to analyze GALNT1 expression across cancer types and at the single-cell resolution. The expression and subcellular localization of GALNT1 in breast cancer were verified using qRT-PCR, Western blot, and immunofluorescence staining. Functional assays were conducted to assess its effects on cell proliferation, migration, and O-glycosylation, while CCK-8 assays were used to evaluate sensitivity to bortezomib. GALNT1 was significantly upregulated in primary breast cancer as well as multiple other malignancies. In vitro experiments demonstrated that GALNT1 promoted breast cancer cell proliferation, migration, and O-glycosylation. Immunofluorescence staining revealed widespread GALNT1 expression in tumor epithelial cells and cancer-associated fibroblasts (CAFs), with colocalization to the Tn antigen. Notably, GALNT1-mediated O-glycosylation was associated with resistance to bortezomib. High GALNT1 expression correlated with increased infiltration of CAFs and M2 macrophages, and reduced CD8⁺ T cell infiltration. Single-cell transcriptomic analysis further confirmed CAF-specific enrichment and elevated epithelial-mesenchymal transition (EMT) scores. GALNT1 is highly expressed in breast cancer, where it promotes tumor progression, bortezomib resistance through O-glycosylation, and immune microenvironment remodeling. The data imply that GALNT1 could represent a novel therapeutic candidate in breast cancer.
Li et al. (Wed,) studied this question.