Liu Xue, Gao Jiujiao, Sun Yan, Zhang Dandan, Liu Tingjiao, Yan Qiu, Yang Xuesong
Biol Chem. 2017 Sep 26;398(10):1119-1126. doi: 10.1515/hsz-2016-0232.
Epithelial cell adhesion molecule (EpCAM) expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin. We also found that effect of N-glycosylation of EpCAM on cell adhesion was regulated via FAK/Akt/Gsk-3β/β-catenin signaling pathway, which further adjusted MMP2/9 expression and activities. Our studies identified the characteristics and function of EpCAM glycosylation sites on breast cancer cell adhesion. These data could potentially clarify molecular regulation of EpCAM by N-glycosylation and intensify our understanding of the utility of glycosylated EpCAM as a target for breast cancer therapy.
上皮细胞粘附分子（EpCAM）在乳腺癌组织中的表达升高，且与癌症转移和细胞粘附相关。尽管EpCAM糖基化被认为与其功能有关，但其N-糖基化对其功能的贡献仍不清楚。在此，我们分析了EpCAM在乳腺癌细胞中的细胞粘附能力。结果显示，EpCAM表达与细胞粘附相关，且EpCAM的N-糖基化突变降低了粘附能力。EpCAM的N-糖基化突变与整合素β1和纤连蛋白水平降低相关。我们还发现，EpCAM的N-糖基化对细胞粘附的影响是通过FAK/Akt/Gsk-3β/β-连环蛋白信号通路调节的，该信号通路进一步调节MMP2/9的表达和活性。我们的研究确定了EpCAM糖基化位点在乳腺癌细胞粘附中的特征和功能。这些数据可能有助于阐明N-糖基化对EpCAM的分子调控，并加深我们对糖基化EpCAM作为乳腺癌治疗靶点效用的理解。
