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AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth

Stress is integral to tumor evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activate the bioenergetic sensor AMP kinase (AMPK), and tumor cells hijack an AMPK-regulated stress response pathway conserved in normal cells, to survive....

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Autores principales: Chhipa, Rishi Raj, Fan, Qiang, Anderson, Jane, Muraleedharan, Ranjithmenon, Huang, Yan, Ciraolo, Georgianne, Chen, Xiaoting, Waclaw, Ronald, Chow, Lionel M., Khuchua, Zaza, Kofron, Matthew, Weirauch, Matthew T., Kendler, Ady, McPherson, Christopher, Ratner, Nancy, Nakano, Ichiro, Dasgupta, Nupur, Komurov, Kakajan, Dasgupta, Biplab
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113057/
https://www.ncbi.nlm.nih.gov/pubmed/29915361
http://dx.doi.org/10.1038/s41556-018-0126-z
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author Chhipa, Rishi Raj
Fan, Qiang
Anderson, Jane
Muraleedharan, Ranjithmenon
Huang, Yan
Ciraolo, Georgianne
Chen, Xiaoting
Waclaw, Ronald
Chow, Lionel M.
Khuchua, Zaza
Kofron, Matthew
Weirauch, Matthew T.
Kendler, Ady
McPherson, Christopher
Ratner, Nancy
Nakano, Ichiro
Dasgupta, Nupur
Komurov, Kakajan
Dasgupta, Biplab
author_facet Chhipa, Rishi Raj
Fan, Qiang
Anderson, Jane
Muraleedharan, Ranjithmenon
Huang, Yan
Ciraolo, Georgianne
Chen, Xiaoting
Waclaw, Ronald
Chow, Lionel M.
Khuchua, Zaza
Kofron, Matthew
Weirauch, Matthew T.
Kendler, Ady
McPherson, Christopher
Ratner, Nancy
Nakano, Ichiro
Dasgupta, Nupur
Komurov, Kakajan
Dasgupta, Biplab
author_sort Chhipa, Rishi Raj
collection PubMed
description Stress is integral to tumor evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activate the bioenergetic sensor AMP kinase (AMPK), and tumor cells hijack an AMPK-regulated stress response pathway conserved in normal cells, to survive. Analysis of The Cancer Genome Atlas (TCGA) data revealed that AMPK isoforms are highly expressed in the lethal human cancer Glioblastoma (GBM). We show that AMPK inhibition reduces viability of patient-derived GBM stem cells (GSCs) and tumors. In stressed (exercised) skeletal muscle, AMPK is activated to cooperate with the cAMP response element binding protein-1 (CREB1) and promote glucose metabolism. We demonstrate that oncogenic stress chronically activates AMPK in GSCs that coopt the AMPK-CREB1 pathway to coordinate tumor bioenergetics through the transcription factors HIF1α and GABPA. Finally, we show that adult mice tolerate systemic deletion of AMPK supporting the utility of AMPK pharmacological inhibitors in the treatment of GBM.
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spelling pubmed-61130572018-12-18 AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth Chhipa, Rishi Raj Fan, Qiang Anderson, Jane Muraleedharan, Ranjithmenon Huang, Yan Ciraolo, Georgianne Chen, Xiaoting Waclaw, Ronald Chow, Lionel M. Khuchua, Zaza Kofron, Matthew Weirauch, Matthew T. Kendler, Ady McPherson, Christopher Ratner, Nancy Nakano, Ichiro Dasgupta, Nupur Komurov, Kakajan Dasgupta, Biplab Nat Cell Biol Article Stress is integral to tumor evolution, and cancer cell survival depends on stress management. We found that cancer-associated stress chronically activate the bioenergetic sensor AMP kinase (AMPK), and tumor cells hijack an AMPK-regulated stress response pathway conserved in normal cells, to survive. Analysis of The Cancer Genome Atlas (TCGA) data revealed that AMPK isoforms are highly expressed in the lethal human cancer Glioblastoma (GBM). We show that AMPK inhibition reduces viability of patient-derived GBM stem cells (GSCs) and tumors. In stressed (exercised) skeletal muscle, AMPK is activated to cooperate with the cAMP response element binding protein-1 (CREB1) and promote glucose metabolism. We demonstrate that oncogenic stress chronically activates AMPK in GSCs that coopt the AMPK-CREB1 pathway to coordinate tumor bioenergetics through the transcription factors HIF1α and GABPA. Finally, we show that adult mice tolerate systemic deletion of AMPK supporting the utility of AMPK pharmacological inhibitors in the treatment of GBM. 2018-06-18 2018-07 /pmc/articles/PMC6113057/ /pubmed/29915361 http://dx.doi.org/10.1038/s41556-018-0126-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Chhipa, Rishi Raj
Fan, Qiang
Anderson, Jane
Muraleedharan, Ranjithmenon
Huang, Yan
Ciraolo, Georgianne
Chen, Xiaoting
Waclaw, Ronald
Chow, Lionel M.
Khuchua, Zaza
Kofron, Matthew
Weirauch, Matthew T.
Kendler, Ady
McPherson, Christopher
Ratner, Nancy
Nakano, Ichiro
Dasgupta, Nupur
Komurov, Kakajan
Dasgupta, Biplab
AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title_full AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title_fullStr AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title_full_unstemmed AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title_short AMP Kinase Promotes Glioblastoma Bioenergetics and Tumor Growth
title_sort amp kinase promotes glioblastoma bioenergetics and tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113057/
https://www.ncbi.nlm.nih.gov/pubmed/29915361
http://dx.doi.org/10.1038/s41556-018-0126-z
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