Abstract A23: AMPK's role in glioblastoma survival: An insight into its regulation on transcription factors and mTOR

Abstract AMP kinase (AMPK) is an evolutionarily conserved enzyme required for adaptive responses to various physiological and pathological conditions. The multisubunit structure and sensitivity to various stresses confer complexity to AMPK function which scores beyond energy sensing. Here we show that inhibition of AMPK reduces viability of patient-derived primary Glioblastoma Multiforme (GBM) lines and tumors. We demonstrate that primary GBM cells coopt the AMPK-CREB1 pathway to coordinate global bioenergetics program through control of the transcription factors HIF1alpha and GABPA. But a growing number of AMPK activators are being developed to treat human diseases such as cancer and diabetes. This may be because AMPK activity can inhibit biosynthetic kinases like mammalian target of rapamycin (mTOR) and acetyl Co-A carboxylase (ACC). We found that AMPK silencing in glioma cells did not affect mTOR or downstream targets. AMPK is not absolutely necessary for mTOR inhibition, suggesting that in certain contexts, activated AMPK and mTOR may coexist. Indeed, this is what we observed in glioblastoma suggesting that basally active AMPK may not be sufficient to put a brake on mTOR. Further analysis of our preliminary data from primary tumor cells on Cap-dependent and well reported procancer IRES dependent translation under tumor microenvironment context will demonstrate significance of AMPK in translational machinery in GBM and will benefit in finding new therapeutic targets. Citation Format: Rishi Raj Chhipa, Biplab Dasgupta. AMPK's role in glioblastoma survival: An insight into its regulation on transcription factors and mTOR. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr A23.