Research Paper Volume 14, Issue 1 pp 316—329
Deglycosylated EpCAM regulates proliferation by enhancing autophagy of breast cancer cells via PI3K/Akt/mTOR pathway
- 1 Department of Biochemistry and Molecular Biology, College of Basic Medicine Sciences, Dalian Medical University, Dalian, China
- 2 Section of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, China
- 3 Department of Clinical Biochemistry, College of Laboratory Science, Dalian Medical University, Dalian, China
Received: January 1, 2021 Accepted: December 7, 2021 Published: January 4, 2022
https://doi.org/10.18632/aging.203795How to Cite
Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Autophagy is an important regulator of cellular homeostasis and its dysregulation often results in cancer. Aberrant glycosylation induced by oncogenic transformation contributes to tumor invasion and metastasis. In a previous study, we have demonstrated that EpCAM, a glycosylation protein, is associated with cell growth and metastasis in breast cancer. But the effect of EpCAM glycosylation on autophagy is not clear. the precise mechanism of regulation remains largely unknown. In this study, breast cancer cells were transfected with N-glycosylation mutation EpCAM plasmid to express deglycosylated EpCAM. The result showed that deglycosylated EpCAM promoted autophagy in breast cancer cells. We further confirmed this conclusion with the activator (Rapamycin, RAP) and inhibitor (Wortmannin) of autophagy. We also found that deglycosylated EpCAM promoted apoptosis and inhibited proliferation through activating autophagy by suppressing Akt/mTOR signaling pathway in breast cancer cells. These findings represent a novel mechanism by which deglycosylated EpCAM inhibits proliferation by enhancing autophagy of breast cancer cells via PI3K/Akt/mTOR pathway. In conclusion, the combination of autophagy modulation and EpCAM targeted therapy is a promising therapeutic strategy in the treatment of breast cancer.