Title:O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2
VOLUME: 16 ISSUE: 9
Author(s):Chenglong Li, Li Deng, Hugang Shen, Qingyou Meng, Aimin Qian, Hongfei Sang, Jiazeng Xia and Xiaoqiang Li
Affiliation:Department of Vascular Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215000, China., Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214002, China.
Keywords:MGMT, MMP2, gastric carcinoma, migration, invasion, metastasis.
Abstract:MGMT plays a key role in many kinds of cancers. However, the molecular
mechanisms of MGMT involvement in gastric cancer (GC) are poorly elucidated. Here,
we investigated the role of MGMT in GC cell migration, invasion and metastatic potential.
Our data showed that MGMT expression was negatively correlated with lymph node
metastasis and late TNM stages. These findings were accompanied by downregulation of
matrix metalloproteinase 2 (MMP2). Loss of MGMT expression induced increases in GC
cell metastasis and invasion potential in vitro and in vivo. These effects were reversed by
inhibition of MGMT and MMP2. MGMT overexpression downregulated MMP2 protein levels, whereas this
effect was counteracted by MGMT siRNA. In summary, MGMT is involved in gastric carcinogenesis via
downregulation of MMP2. The MGMT/MMP2 pathway plays an essential role in GC metastasis and may be a
potential therapeutic target for GC treatment.
