By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis.

Jiujiao Gao,Fan Yang,Xue Liu,Qiu Yan,Tingjiao Liu,Xuesong Yang

doi:10.18632/oncotarget.4551

Jiujiao Gao, Fan Yang + Show 4 more

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https://doi.org/10.18632/oncotarget.4551

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Abstract

Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane protein that is expressed in the majority of normal epithelial tissues and is overexpressed in most epithelial cancers including breast cancer, where it plays an important role in cancer progression. However, the mechanism by which EpCAM promotes the progression of breast cancer is not understood. In this study, we found that EpCAM expression was increased in tumor tissue from breast cancer patients compared to healthy patients. Overexpression of EpCAM in breast cancer cells enhanced tumor cell growth in vitro and increased invasiveness, whereas small interfering RNA-mediated silencing of EpCAM (si-EpCAM) had the opposite effect. EpCAM knockdown led to decreased phosphorylation of Raf and ERK, suppression of malignant behavior of breast cancer cells, and inhibition of the Ras/Raf/ERK signaling pathway. Furthermore, si-EpCAM-mediated invasion and metastasis of breast carcinoma cells required the downregulation of matrix metalloproteinase-9 (MMP-9) through inhibition of this signaling pathway. In conclusion, our data show that knockdown of EpCAM can inhibition breast cancer cell growth and metastasis via inhibition of the Ras/Raf/ERK signaling pathway and MMP-9.

Highlights

Breast cancer is a malignant tumor that originates from healthy mammary gland cells, and is most frequent among women aged between 50 and 70 years [1]
Epithelial cell adhesion molecule (EpCAM) expression was higher in estrogen receptor-negative (ER-) cases (84.6% in ERcancers versus 74.5% in ER+ cancers, P < 0.0001; Table 1) and human epidermal growth factor receptor 2-positive (HER2+) cases (82.5% in HER2+ cancers versus 74.6% in HER2- cancers, P < 0.05; Table 1)
Through the results of table 1, we demonstrate that EpCAM was tumor-associated molecular and associated with the progression of breast cancer

Summary

Introduction

Breast cancer is a malignant tumor that originates from healthy mammary gland cells, and is most frequent among women aged between 50 and 70 years [1]. Epithelial cell adhesion molecule (EpCAM) is a glycosylated, type I transmembrane protein, which is overexpressed in various neoplasms such as breast cancer [3], hepatocellular carcinoma (HCC) [4], glioma [5], and colorectal cancer [6], and is used as a diagnostic and prognostic marker. Increasing clinical evidence has confirmed that EpCAM is involved in cancer progression and is associated with a poor prognosis. The overexpression of EpCAM has been associated with a poor prognosis in patients with pancreatic cancer and HCC [7, 8]. Emerging evidence suggests that EpCAM may be a critical factor in tumor development, progression, and metastasis [9,10,11]. Another report demonstrated the positive roles of EpCAM in the regulation of cell growth and the self-renewal of human keratinocytes [13]

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