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http://dx.doi.org/10.14348/molcells.2021.2179

Metallothionein MT1M Suppresses Carcinogenesis of Esophageal Carcinoma Cells through Inhibition of the Epithelial-Mesenchymal Transition and the SOD1/PI3K Axis  

Li, Dandan (Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University)
Peng, Weiyan (Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University)
Wu, Bin (Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University)
Liu, Huan (Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University)
Zhang, Ruizhen (Department of Otolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University)
Zhou, Ruiqin (Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University)
Yao, Lijun (Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University)
Ye, Lin (Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University)
Publication Information
Molecules and Cells / v.44, no.4, 2021 , pp. 267-278 More about this Journal
Abstract
Metallothionein (MT1M) belongs to a family of cysteinerich cytosolic protein and has been reported to be a tumor suppressor gene in multiple cancers. However, its role in esophageal carcinoma carcinogenesis remains unclear. In this study, MT1M expression was correlated with tumor type, stage, drinking and smoking history, as well as patient survival. We also studied the regulation and biological function of MT1M in esophageal squamous cell carcinoma (ESCC). We have found that MT1M is significantly downregulated in ESCC tissues compared with adjacent non-cancer tissues. Furthermore, restoration of expression by treatment with the demethylation agent A + T showed that MT1M downregulation might be closely related to hypermethylation in its promoter region. Over-expression of MT1M in ESCC cells significantly altered cell morphology, induced apoptosis, and reduced colony formation, cell viability, migration and epithelial-mesenchymal transition. Moreover, based on reactive oxygen species (ROS) levels, a superoxide dismutase 1 (SOD1) activity assay and protein analysis, we verified that the tumor-suppressive function of MT1M was at least partially caused by its upregulation of ROS levels, downregulation of SOD1 activity and phosphorylation of the SOD1 downstream pathway PI3K/AKT. In conclusion, our results demonstrated that MT1M was a novel tumor-suppressor in ESCC and may be disrupted by promoter CpG methylation during esophageal carcinogenesis.
Keywords
esophageal squamous cell carcinoma; MT1M; PI3K/AKT; SOD1; tumor suppressor;
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