Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death

Enyu Rao; Yuwen Zhang; Ganqian Zhu; Jiaqing Hao; Xuan-Mai T Persson; Nejat K Egilmez; Jill Suttles; Bing Li

doi:10.18632/oncotarget.3501

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Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death

Journal article

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Peer reviewed

Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death

Enyu Rao, Yuwen Zhang, Ganqian Zhu, Jiaqing Hao, Xuan-Mai T Persson, Nejat K Egilmez, Jill Suttles and Bing Li

Oncotarget, Vol.6(10), pp.7944-7958

04/10/2015

DOI: 10.18632/oncotarget.3501

PMCID: PMC4480727

PMID: 25760243

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Abstract

A number of studies have linked AMPK, a major metabolic sensor coordinating of multiple cellular functions, to tumor development and progression. However, the exact role of AMPK in tumor development is still controversial. Here we report that activation of AMPK promotes survival and anti-tumor function of T cells, in particular CD8+ T cells, resulting in superior tumor suppression in vivo. While AMPK expression is dispensable for T cell development, genetic deletion of AMPK promotes T cell death during in vitro activation and in vivo tumor development. Moreover, we demonstrate that protein phosphatases are the key mediators of AMPK-dependent effects on T cell death, and inhibition of phosphatase activity by okadaic acid successfully restores T cell survival and function. Altogether, our data suggest a novel mechanism by which AMPK regulates protein phosphatase activity in control of survival and function of CD8+ T cells, thereby enhancing their role in tumor immunosurveillance.

AMP-Activated Protein Kinases - deficiency

AMP-Activated Protein Kinases - metabolism

CD8-Positive T-Lymphocytes - enzymology

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - metabolism

Cell Death - physiology

Cell Line, Tumor

Cell Survival - physiology

Humans

Phosphoprotein Phosphatases - metabolism

Details

Title: Subtitle: Deficiency of AMPK in CD8+ T cells suppresses their anti-tumor function by inducing protein phosphatase-mediated cell death
Creators: Enyu Rao - Hormel (United States)
Yuwen Zhang - University of Minnesota
Ganqian Zhu - Hormel (United States)
Jiaqing Hao - Hormel (United States)
Xuan-Mai T Persson - Mayo Clinic
Nejat K Egilmez - University of Louisville
Jill Suttles - University of Louisville
Bing Li - Hormel (United States)
Resource Type: Journal article
Publication Details: Oncotarget, Vol.6(10), pp.7944-7958
DOI: 10.18632/oncotarget.3501
PMID: 25760243
PMCID: PMC4480727
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Grant note: R56 AI048850 / NIAID NIH HHS R01 CA18098601A1 / NCI NIH HHS UL1 TR000135 / NCATS NIH HHS U24DK100469 / NIDDK NIH HHS R01 AI048850 / NIAID NIH HHS R21 AI048850 / NIAID NIH HHS 5P30DK50456 / NIDDK NIH HHS UL1TR000135 / NCATS NIH HHS R01 CA17767901A1 / NCI NIH HHS U24 DK100469 / NIDDK NIH HHS P30 DK050456 / NIDDK NIH HHS
Language: English
Date published: 04/10/2015
Academic Unit: Pathology; Surgery
Record Identifier: 9984696540102771

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