Deglycosylated EpCAM regulates proliferation by enhancing autophagy of breast cancer cells via PI3K/Akt/mTOR pathway.

Tingjiao Liu,Qijun Wang,Liu Yang,Qian Zhao,Xuesong Yang,Qiu Yan,Xiaohua Huang,Fan Yang

doi:10.18632/aging.203795

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.

Highlights

Breast cancer (BC) is the second most common malignancy among women [1]
To elucidate glycosylation of Epithelial cell adhesion molecule (EpCAM) in BC on autophagy, an EpCAM overexpression plasmid and small interfering RNA-mediated silencing of EpCAM were used to increase and reduce EpCAM expression in MCF-7 and MDA-MB-231 breast cancer cell lines, respectively
Our findings proved that glycosylated EpCAM might regulate the apoptosis by influencing autophagy in breast cancer cells

Summary

Introduction

The main cause of high mortality rate in BC is cancer recurrence, which origin from the metastasis of dormant tumor cells [2, 3]. Surgical operation is the main treatment for breast cancer, which is effective for early stage of BC. For the advanced, incurable stage of BC, transitional chemotherapeutic agents do not produce good results [4, 5]. EpCAM knockdown promoted apoptosis and raised the cytotoxic effect of 5Fluorouracil in breast cancer cells through MAPK signaling pathway [13].

Methods

Results

Conclusion