Effect Of Epithelial Cell Adhesion Molecule On Proliferation And Metastasis In Hypopharyngeal Carcinoma And The Mechanism

Hypopharyngeal carcinoma, one of the most common forms of head and neck squamous cell carcinoma (HNSCC), brings about substantial morbidity and mortality annually. The predominant therapy of hypopharyngeal carcinoma is still confined to surgery and the additional treatment remains radiotherapy and chemotherapy. Although surgical techniques and anticancer agents have been advanced, the overall survival rates have not been significantly improved during the last two decades. Therefore, identification of the related targeted factors and the potential mechanism of hypopharyngeal carcinoma metastasis and proliferation are important for the survival of patients.Epithelia cell adhesion molecule (EpCAM, also known as CD326), a39-42kDa, type I trans-membrane glycoprotein, consists of an extracellular domain (EpEX), a single transmembrane domain and a short26-amino acid intracellular domain (EpICD). EpCAM is overexpressed by most human epithelial carcinomas, such as breast, colorectal, prostate, hepatic, head and neck carcinomas, and its overexpression in these cancers is associated with proliferation and neoplastic transformation. Recently, targeting EpCAM might become a promising approach for cancer therapy. However, the research concerning the effect of EpCAM in hypopharyngeal carcinomas is few. In our present study, we illustrated the possible role of EpCAM in hypopharyngeal carcinoma.Objective To explore the expression of EpCAM in hypopharyngeal carcinoma, and the relationship of EpCAM expression and hypopharyngeal carcinoma proliferation and metastasis.Methods Forty hypopharyngeal carcinoma tissue samples and ten normal squamous epithelium tissue samples were obtained for immunohistochemistry assay. Hypopharyngeal carcinoma FaDu cell line was treated with EpCAM siRNA. The expression of EpCAM was detected by Western Blot and Real Time PCR, respectively. Cell invasion and migration assays were performed using Transwel chambers; Cell proliferation was examined by MTT; In vitro colony formation was performed by plate colony assay. Western Blot assay was conducted to detect E-cadherin, a-catenin. and p-catenin expression.Results EpCAM was overexpressed in primary hypopharyngeal carcinoma and EpCAM overexpression was correlated with tumor size and lymph node metastasis in hypopharyneal carcinoma. Down-regulation of EpCAM by EpCAM siRNA resulted in decrease of invasion and migration of FaDu cells, which had high endogenous EpCAM expression. And EpCAM down-regulation significantly suppressed in vitro proliferation and colony formation abilities of hypopharyngeal carcinoma cells. Down-regulation of EpCAM expression increased the E-cadherin, a-catenin and P-catenin expression of the insoluble protein. EpCAM down-regulation significantly inhibited β-catenin expression in nuclear.Conclusion The knockdown of EpCAM inhibits the invasion, migration, and colony formation abilities of FaDu cells, and its mechanism is related to the regulation of E-cadherin, a-catenin and β-catenin, EpCAM may be a promising gene therapy target for hypopharyngeal carcinoma.