• NCAM and polysialylated NCAM are aberrantly regulated in breast cancer cells and upregulated during EMT in normal breast epithelial cells.
• NCAM-140 overexpression induces EMT and promotes proliferation and migration via the β-catenin/slug pathway.
• Polysialic acid modification of NCAM modulates cell adhesion and motility through the EGFR/STAT3 pathway.
• The study clarifies distinct signaling mechanisms by which NCAM and its polysialylation regulate breast epithelial cell behaviors, highlighting their significance in tumor development.