MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer

Abstract

BackgroundOverexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients’ poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients’ prognosis.MethodsWe checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software.ResultsMTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What’s more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival.ConclusionsWe revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma.

RETRACTED ARTICLE: TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells

“…Despite recent advances in diagnosis and treatment, the prognosis of lung cancer is still poor [ 3 ]. Therefore, a better understanding of which pathways or proteins are active in lung tumor progression will contribute to the development of early detection and targeted therapy for lung cancer [ 4 – 6 ].…”

Functions of EpCAM in physiological processes and diseases (Review)

“…Originally identified as a novel tumor-specific cell surface antigen following immunization of mice with cancer cells in 1970s ( 1 ), EpCAM has been known to be highly expressed in a variety of epithelial carcinomas ( 104 ). EpCAM is also highly expressed in acute myeloid leukemia (AML), and EpCAM-positive cells may be leukemia stem cells which could promote leukemic progression ( 105 ).…”

Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway

“…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 specifically expressed in epithelial tissue and overexpressed in a large variety of human epithelial-derived neoplasms, including cancer of the tongue 10 , thyroid 11 , prostate 12 – 14 , oesophagus 15 , liver 16 , 17 , colon 18 , breast 19 , 20 , ovary 21 , pancreas 22 , gallbladder 23 , lung 24 , stomach 25 and kidney 26 . Recent studies have revealed that EpCAM is involved in cell signalling, migration, proliferation and differentiation, as well as in metastasis and cancer stem cells 27 .…”