Astrocyte elevated gene-1 interacts with Akt isoform 2 to control glioma growth, survival, and pathogenesis.

摘要: The oncogene astrocyte elevated gene-1 (AEG-1; MTDH) is highly expressed in glioblastoma multiforme (GBM) and many other types of cancer, where it activates multiple signaling pathways that drive proliferation, invasion, angiogenesis, chemoresistance, radioresistance, metastasis. AEG-1 the Akt pathway c-Myc are positive regulators transcription, generating a feedback loop between regulating tumorigenesis. Here, we describe GBM cells direct interaction an internal domain PH Akt2, major driver GBM. Expression Akt2 contribute to tumor cell survival, invasion. Clinically, silico gene expression immunohistochemical analyses patient specimens showed correlated with progression reduced survival. AEG-1-Akt2 prolonged stabilization phosphorylation at S474, downstream cascades enable proliferation Disrupting by competitive binding Akt2-PH led viability When combined silencing, conditional markedly increased survival orthotopic mouse model human Our study uncovers novel molecular mechanism which augments glioma offers rationale block function as treatment.