Deletion and downregulation of MTAP contribute to the motility of esophageal squamous carcinoma cells.

Abstract

Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, with a low 5-year overall survival rate. In previous studies, we and others have found that 9p21.3 was the most frequently deleted region in ESCC. The MTAP gene, which is located close to CDKN2A/B in 9p21.3, encodes methylthioadenosine phosphorylase. This enzyme plays an important role during the process of adenosine transfer. In the present study, we found that MTAP is deleted at the genomic level in 19.1% (64/341) of primary ESCC tumors, and decreased mRNA and protein expression were present in 31.1% (28/90) and 33.3% (6/18) of ESCCs, respectively. Further statistical analysis showed a positive correlation between deletion and decreased mRNA expression of MTAP in the ESCC tissues tested (coefficient: 0.826; P=1.17×10−23). Knockdown of MTAP expression using small interfering RNA-mediated silencing promoted the invasion and migration of ESCC cells. Also, overexpression of MATP using pcDNA3.1-MTAP plasmid decreased the cell invasion and migration. At the molecular level, MTAP knockdown downregulated E-cadherin and p-GSK3β but upregulated Slug expression. Our results indicated that MTAP deletion results in the decreased expression in ESCCs and that it plays a role in promoting the mobility and inducing the epithelial-to-mesenchymal transition of ESCC cells via the GSK3β/Slug/E-cadherin axis. The data suggest that MTAP might function as a tumor suppressor gene in ESCC.