Abstract
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. However, its expression profile and biological function in nasopharyngeal carcinoma (NPC) remains unclear. In this study, higher expression of EpCAM was found in NPC samples compared with non-cancer nasopharyngeal mucosa by qRT-PCR. Additionally, immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival. Multivariate survival analysis identified high EpCAM expression as an independent prognostic factor. Ectopic EpCAM expression in NPC cells promoted epithelial-mesenchymal transition (EMT), induced a cancer stem cell (CSC)-like phenotype, and enhanced metastasis in vitro and in vivo without an effect on cell proliferation. Notably, EpCAM overexpression reduced PTEN expression and increased the level of AKT, mTOR, p70S6K and 4EBP1 phosphorylation. Correspondingly, an AKT inhibitor and rapamycin blocked the effect of EpCAM on NPC cell invasion and stem-like phenotypes, and siRNA targeting PTEN rescued the oncogenic activities in EpCAM knockdown NPC cells. Our data demonstrate that EpCAM regulates EMT, stemness and metastasis of NPC cells via the PTEN/AKT/mTOR pathway.
Highlights
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation
EpCAM is frequently upregulated in nasopharyngeal carcinoma (NPC) tissues and cells In the current study, EpCAM expression levels were evaluated in 22 snap-frozen NPC tissues and 14 noncancerous nasopharyngitis (NP) tissues using quantitative real-time PCR, and the results showed that EpCAM was significantly upregulated in tumour tissues in comparison with non-tumour tissues (P < 0.01) (Fig. 1a)
In light of the obvious connection between EpCAM expression and distant metastasis in clinical samples, we examined the potential regulation of EpCAM on epithelial-mesenchymal transition (EMT), which is considered to be a critical process in cancer metastasis
Summary
Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. Immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival. Ectopic EpCAM expression in NPC cells promoted epithelial-mesenchymal transition (EMT), induced a cancer stem cell (CSC)-like phenotype, and enhanced metastasis in vitro and in vivo without an effect on cell proliferation. EpCAM is a type I transmembrane glycoprotein with an ectodomain, one transmembrane domain, and a cytoplasmic domain of 26 residues[8,9] This glycoprotein is expressed in epithelial tissue and overexpressed in a large variety of Official journal of the Cell Death Differentiation Association. EpCAM is one of the best studied cancerassociated antigens, its expression profile, biological function and clinical significance in NPC have not been reported until now. The aim of this study was to explore the expression profile of EpCAM and its role in NPC aggressiveness
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