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Metallothionein 1M (MT1M) inhibits lung adenocarcinoma cell viability, migration, and expression of cell mobility-related proteins through MDM2/p53/MT1M signaling
- Source :
- Translational Cancer Research
- Publication Year :
- 2020
- Publisher :
- AME Publishing Company, 2020.
-
Abstract
- Background Metallothionein 1M (MT1M) functions to regulate cell proliferation and cancer metastasis. This study assessed the effects of MT1M overexpression and mouse double minute 2 homolog (MDM2) knockdown on the regulation of non-small cell lung cancer A549 cell viability, migration, and protein expression in vitro and explored the underlying molecular events. Methods A549 cells were stably infected with lentivirus carrying MT1M cDNA or transiently transfected MDM2 siRNA and/or treated with the p53 inhibitor for the assessment of changes in cell viability, wound healing, Transwell migration, and qRT-PCR and Western blot assays. Luciferase reporter assay was performed to investigate p53 binding to the MT1M promoter. Results The data showed that MT1M overexpression inhibited A549 cell viability and migration capacity in vitro, whereas the p53 inhibitor reversed the inhibition of A549 cell viability and migration caused by MT1M overexpression as well as the expression of MMP2, MMP9, and MMP14. Furthermore, knockdown of MDM2, an upstream inhibitor of p53 activity, was able to reduce A549 cell viability, migration, and protein expression. Thus, MDM2 knockdown had synergistic effects with MT1M overexpression on the suppression of A549 cell viability, migration, and protein expression. Conclusions In conclusion, MDM2 can bind to and phosphorylate p53 protein to inactivate the protein, thereby reducing MT1M expression and leading to tumor cell proliferation and migration.
- Subjects :
- p53
Cancer Research
Lung
Chemistry
Metallothionein 1M (MT1M)
proliferation
Adenocarcinoma cell
Metallothionein 1M
migration
medicine.anatomical_structure
Oncology
Cell Mobility
medicine
Cancer research
Radiology, Nuclear Medicine and imaging
Mdm2 p53
Original Article
mouse double minute 2 homolog (MDM2)
Subjects
Details
- Language :
- English
- ISSN :
- 22196803 and 2218676X
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Translational Cancer Research
- Accession number :
- edsair.doi.dedup.....2788eb5effe97796ac36dc4acaff8bd2