Wnt信号通路
糖基化
CD44细胞
下调和上调
癌症研究
癌症
连环素
癌细胞
细胞生物学
信号转导
生物
基因敲除
化学
体外
生物化学
细胞凋亡
基因
遗传学
作者
Junchang Zhang,Han Wang,Jing Wu,Cheng Yuan,Songyao Chen,Shuhao Liu,Mingyu Huo,Changhua Zhang,Yulong He
摘要
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 (GALNT1) is frequently upregulated in gastric cancer and is correlated with poor survival. Overexpression of GALNT1 promoted, whereas knockdown suppressed proliferation, migration, and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, GALNT1 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 GALNT1 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.
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