Tn antigen promotes breast cancer metastasis via impairment of CASC4

• DOI: 10.1002/cbin.12077
• Publication Date: 2023-07-26T13:19:56Z
• Authors: Ruijun Li; Xichen Dong; Shibin Chen; Jingyu Tan; Xiangyu Chen; Jian Liu; Tao Wen; Xiaoli Ru
• Keywords: CA 15-3

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being leading cause death. Tn antigen, a tumor-associated carbohydrate was frequently detected breast cancer, but its exact role metastasis has not been well elucidated. Here we investigated impact antigen expression on underlying mechanisms. The induced two cell lines by deleting T-synthase or Cosmc, both which are required for normal O-glycosylation. It showed that Tn-expressing cells promoted epithelial-mesenchymal transition (EMT) metastatic features as compared to Tn(-) control vitro vivo. Mechanistically, found susceptibility candidate 4 (CASC4), heavily O-glycosylated protein, significantly downregulated Tn(+) cells. Overexpression CASC4 suppressed Tn-induced activation EMT via inhibition Cdc42 signaling. Furthermore, confirmed O-glycosylation essential functional because defective (mutant CASC4, lacks nine sites) exerted marginal metastatic-suppressing effects comparison WT CASC4. Collectively, these data suggest Tn-mediated aberrant contributes impairment function.