Hypoxia modulates stem cell properties and induces EMT through N-glycosylation of EpCAM in breast cancer cells

Zhang, DD; Yang, L; Liu, X; Gao, JJ; Liu, TJ; Yan, Q; Yang, XS

Yang, XS (reprint author), Dalian Med Univ, Dept Biochem & Mol Biol, Liaoning Prov Core Lab Glycobiol & Glycoengn, Dalian 116044, Peoples R China.

JOURNAL OF CELLULAR PHYSIOLOGY, 2020; 235 (4): 3626

Abstract

Epithelial cell adhesion molecule (EpCAM), which is a transmembrane glycoprotein, is related to tumor progression. We demonstrated that EpCAM plays important roles in proliferation, apoptosis, and metastasis during breast cancer (BC) progression. But the role of N-glycosylation in EpCAM in tumor aggressiveness is not clear. Here, we evaluated the role of N-glycosylation of EpCAM in stemness and epithelial-mesenchymal transition (EMT) characteristics. EpCAM overexpression increases the expression of stemness markers (NANOG?SOX2, and OCT4) and EMT markers (N-cadherin and vimentin) under the condition of hypoxia in BC. Knockdown of EpCAM and mutation of N-glycosylation of EpCAM maintained in severe hypoxia lead to a significant reduction of stemness/EMT markers. In addition, we found that N-glycosylation of EpCAM is a crucial factor during this process. This demonstrates that EpCAM has a novel regulatory role in stemness/EMT dependence of hypoxia-inducible factor 1-alpha via regulating nuclear factor kappa B in BC cells. Hence, our study reveals EpCAM glycosylation modification as a new regulator of stemness/EMT under hypoxic in BC and points out EpCAM as a potential therapeutic target.

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