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.
Keywords: MGMT, MMP2, gastric carcinoma, migration, invasion, metastasis.
Anti-Cancer Agents in Medicinal Chemistry
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:
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.
Export Options
About this article
Cite this article as:
Li Chenglong, Deng Li, Shen Hugang, Meng Qingyou, Qian Aimin, Sang Hongfei, Xia Jiazeng and Li Xiaoqiang, O-6-methylguanine-DNA Methyltransferase Inhibits Gastric Carcinoma Cell Migration and Invasion by Downregulation of Matrix Metalloproteinase 2, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1871520615666150914114455
DOI https://dx.doi.org/10.2174/1871520615666150914114455 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Discovery of Lead compounds targeting transcriptional regulation
Transcriptional regulation plays key physiological functions in body growth and development. Transcriptional dysregulation is one of important biomarkers of tumor genesis and progression, which is involved in regulating tumor cell processes such as cell proliferation, differentiation, and apoptosis. Additionally, it plays a pivotal role in angiogenesis and promotes tumor metastasis ...read more
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Innovative targets in medicinal chemistry
Medicinal chemistry continuously evolves in response to emerging healthcare needs and advancements in scientific understanding. This special issue explores the current landscape of innovative targets in medicinal chemistry, highlighting the quest for novel therapeutic avenues. From traditional drug targets such as enzymes and receptors to emerging targets like protein-protein interactions ...read more
Metalloenzymes and Cancer: Μetalloenzyme Ιnhibitors and Artificial Metalloenzymes as anti-cancer agents
Metalloenzymes are enzymes containing metal ions, which are directly bound to the enzyme and play a role in promoting catalysis. About one-third of all enzymes known so far are metalloenzymes [1]. Metalloenzymes are central to a wide range of essential biological activities, including nucleic acid modification, protein degradation, and many ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Copper Complexes of Bioactive Ligands with Superoxide Dismutase Activity
Mini-Reviews in Medicinal Chemistry The Integral Nuclear Membrane Protein Nurim Plays a Role in the Suppression of Apoptosis
Current Molecular Medicine Ellagitannins, Gallotannins and their Metabolites- The Contribution to the Anti-Inflammatory Effect of Food Products and Medicinal Plants
Current Medicinal Chemistry Imatinib Dosing in Gastrointestinal Stromal Tumors (GISTs): When, How Much, and How Long?
Current Clinical Pharmacology The Therapeutic Potential of Targeting Autophagy in the Treatment of Cancer
Current Cancer Drug Targets Targeting Cyclooxygenase and Nitric Oxide Pathway Cross-Talk: A New Signal Transduction Pathway for Developing More Effective Anti- Inflammatory Drugs
Current Signal Transduction Therapy Cucurbitacins as Anticancer Agents: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery The Gut Mucosa as a Site for Induction of Regulatory T-Cells
Current Pharmaceutical Design Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
Current Pharmaceutical Design Anti-cancer Therapies in High Grade Gliomas
Current Proteomics Management of Colorectal Cancer Using Nanocarriers-based Drug Delivery for Herbal Bioactives: Current and Emerging Approaches
Current Pharmaceutical Biotechnology Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways
Current Molecular Medicine Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed
Current Drug Targets Construction of RNA Methylation Modification-immune-related lncRNA Molecular Subtypes and Prognostic Scoring System in Lung Adenocarcinoma
Current Medicinal Chemistry Development on PEG-modified Poly (Amino Acid) Copolymeric Micelles for Delivery of Anticancer Drug
Anti-Cancer Agents in Medicinal Chemistry High Therapeutic Potential for Systemic Delivery of a Liposomeconjugated Herpes Simplex Virus
Current Cancer Drug Targets Bromodomain-Containing Protein 4: A Druggable Target
Current Drug Targets Bioactive Loaded Lipid-based Nanostructures: A Novel Insight for Age-related Neurodegeneration
Current Molecular Medicine Agronomic Cultivation, Chemical Composition, Functional Activities and Applications of Pereskia Species – A Mini Review
Current Medicinal Chemistry Hyaluronan/Hyaladherins - a Promising Axis for Targeted Drug Delivery in Cancer
Current Drug Delivery