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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Adult
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Animals
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Cadherins / metabolism
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Cell Cycle Proteins
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Cell Line, Tumor
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Cell Movement / drug effects
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Epithelial Cell Adhesion Molecule / antagonists & inhibitors
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Epithelial Cell Adhesion Molecule / genetics
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Epithelial Cell Adhesion Molecule / metabolism*
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Epithelial-Mesenchymal Transition
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Female
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Humans
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Kaplan-Meier Estimate
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Male
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Mice
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Mice, Nude
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Middle Aged
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Nasopharyngeal Carcinoma / metabolism
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Nasopharyngeal Carcinoma / mortality
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Nasopharyngeal Carcinoma / pathology*
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Nasopharyngeal Neoplasms / metabolism
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Nasopharyngeal Neoplasms / mortality
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Nasopharyngeal Neoplasms / pathology*
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PTEN Phosphohydrolase / antagonists & inhibitors
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism*
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Phosphoproteins / metabolism
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Proportional Hazards Models
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA Interference
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RNA, Small Interfering / metabolism
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Signal Transduction / drug effects
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Sirolimus / pharmacology
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TOR Serine-Threonine Kinases / antagonists & inhibitors
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TOR Serine-Threonine Kinases / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Cadherins
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Cell Cycle Proteins
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EIF4EBP1 protein, human
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Epithelial Cell Adhesion Molecule
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Phosphoproteins
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RNA, Small Interfering
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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PTEN Phosphohydrolase
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PTEN protein, human
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Sirolimus