MAGEA6 promotes human glioma cell survival via targeting AMPKα1.

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.