Astrocyte elevated gene-1 induces protective autophagy
作者： S. K. Bhutia , T. P. Kegelman , S. K. Das , B. Azab , Z.-z. Su
关键词:
摘要: Astrocyte-elevated gene-1 (AEG-1) expression increases in multiple cancers and plays a crucial role oncogenic transformation angiogenesis, which are essential components tumor cell development, growth, progression to metastasis. Moreover, AEG-1 directly contributes resistance chemotherapeutic drugs, another important hallmark of aggressive cancers. In the present study, we document that mediates protective autophagy, an regulator cancer survival under metabolic stress apoptosis, may underlie its significant cancer-promoting properties. induces noncanonical autophagy involving increase ATG5. decreases ATP/AMP ratio, resulting diminished cellular metabolism activation AMP kinase, AMPK/mammalian target rapamycin-dependent autophagy. Inhibition AMPK by siAMPK or compound C ATG5, ultimately attenuating AEG-1–induced protects normal cells from serum starvation-induced death through inhibition results death. We also show AEG-1–mediated chemoresistance is because decrease chemosensitization cells. summary, study reveals previously unknown aspect function identifying it as potential feature contribute tumor-promoting
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