Related Experiment Videos
MAGEA6 promotes human glioma cell survival via targeting AMPKα1
Si-Jian Pan1, Jie Ren1, Hong Jiang1
1Department of Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, China.
Abstract:
Melanoma antigen A6 (MAGEA6)/TRIM28 complex is a cancer-specific ubiquitin ligase, which degradates tumor suppressor protein AMP-activated protein kinase (AMPK). We show that MAGEA6 is uniquely expressed in human glioma tissues and cells, which is correlated with AMPKα1 downregulation. It is yet absent in normal brain tissues and human astrocytes/neuronal cells. MAGEA6 knockdown by targeted-shRNA in glioma cells restored AMPKα1 expression, causing mTORC1 in-activation and cell death/apoptosis. Reversely, AMPKα1 knockdown or mutation ameliorated glioma cell death by MAGEA6 shRNA. In vivo, Glioma xenograft tumor growth in mice was largely inhibited following expressing MAGEA6 shRNA. AMPKα1 upregulation and mTORC1 inhibition were observed in MAGEA6 shRNA-bearing xenograft tissues. Collectively, MAGEA6 promotes glioma cell survival possibly via targeting AMPKα1.
Insights
Melanoma antigen A6 (MAGEA6) promotes glioma survival by degrading AMP-activated protein kinase (AMPK). Inhibiting MAGEA6 in glioma cells and tumors restores AMPK, leading to cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The Melanoma antigen A6 (MAGEA6)/TRIM28 complex functions as a cancer-specific ubiquitin ligase.
- This complex targets the tumor suppressor protein AMP-activated protein kinase (AMPK) for degradation.
Purpose of the Study:
- To investigate the role of MAGEA6 in glioma development and survival.
- To explore the relationship between MAGEA6 expression and AMPKα1 levels in glioma.
Main Methods:
- Analyzing MAGEA6 expression in human glioma tissues and cells versus normal brain tissues.
- Utilizing MAGEA6 knockdown via targeted shRNA in glioma cells and in vivo xenograft models.
- Assessing AMPKα1 expression, mTORC1 activity, and cell death/apoptosis following MAGEA6 manipulation.
Main Results:
- MAGEA6 is uniquely expressed in human glioma tissues and cells, correlating with AMPKα1 downregulation.
- MAGEA6 knockdown restored AMPKα1, inactivated mTORC1, and induced glioma cell death/apoptosis.
- In vivo, MAGEA6 shRNA significantly inhibited glioma xenograft growth, with observed AMPKα1 upregulation and mTORC1 inhibition.
Conclusions:
- MAGEA6 promotes glioma cell survival by targeting and degrading AMPKα1.
- Targeting the MAGEA6/AMPKα1 axis presents a potential therapeutic strategy for glioma.