NEU4-mediated desialylation enhances the activation of the oncogenic receptors for the dissemination of ovarian carcinoma

We identified neuraminidase 4 (NEU4), that hydrolyzes terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In addition, we for the first time revealed that the plasma membrane-localized NEU4 isoform 2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveals a functionally important glycosite on EGFR for its abnormal activation in cancer.