GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway

Abstract

O-glycosylation is a widespread post-translational modification of proteins. Aberrant O-glycosylation is a hallmark of cancer. Here, we show that the polypeptide N-acetylgalactosamine-transferase 1 (<i>GALNT1</i>) is frequently upregulated in gastric cancer and is correlated with poor survival. Overexpression of <i>GALNT1</i> promoted, whereas knockdown suppressed proliferation, migration, and invasion of gastric cancer cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, <i>GALNT1</i> enhances aberrant initiation of O-glycosylation and results in CD44 glycoproteins modified with abundant Tn antigens, thereby activating the Wnt/β-catenin signaling pathway. Collectively, this study demonstrates that <i>GALNT1</i> overexpression in gastric cancer promotes the Wnt/β-catenin signaling pathway via abnormal O-glycosylation of CD44 to enhance malignancy, providing a novel strategy for the development of therapeutic reagents against gastric cancer.