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AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation

Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca(2+)/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in...

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Autores principales: Chen, Min-Bin, Liu, Yuan-Yuan, Cheng, Li-Bo, Lu, Jian-Wei, Zeng, Ping, Lu, Pei-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458207/
https://www.ncbi.nlm.nih.gov/pubmed/28423719
http://dx.doi.org/10.18632/oncotarget.16126
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author Chen, Min-Bin
Liu, Yuan-Yuan
Cheng, Li-Bo
Lu, Jian-Wei
Zeng, Ping
Lu, Pei-Hua
author_facet Chen, Min-Bin
Liu, Yuan-Yuan
Cheng, Li-Bo
Lu, Jian-Wei
Zeng, Ping
Lu, Pei-Hua
author_sort Chen, Min-Bin
collection PubMed
description Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca(2+)/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in human gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p-AMPKα, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation. Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in human gastric cancer cell lines (AGS, HGC-27, and SNU601). Intriguingly, Ppm1E knockdown by shRNA induced AMPK activation, mTORC1 inactivation, and proliferation inhibition in AGS cells. On the other hand, forced over-expression of Ppm1E induced further AMPK inhibition and mTORC1 activation to enhance AGS cell proliferation. Remarkably, microRNA-135b-5p (“miR-135b-5p”), an anti-Ppm1E microRNA, was downregulated in both human gastric cancer tissues and cells. Reversely, miR-135b-5p exogenous expression caused Ppm1E depletion, AMPK activation, and AGC cell proliferation inhibition. Together, Ppm1E upregulation in human gastric cancer is important for cell proliferation, possible via regulating AMPK-mTOR signaling.
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spelling pubmed-54582072017-06-08 AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation Chen, Min-Bin Liu, Yuan-Yuan Cheng, Li-Bo Lu, Jian-Wei Zeng, Ping Lu, Pei-Hua Oncotarget Research Paper Activation of AMP-activated protein kinase (AMPK) is a valuable anti-cancer strategy. In the current study, we tested expression and potential function of Ca(2+)/calmodulin-dependent protein kinase phosphatase (Ppm1E), an AMPKα phosphatase, in human gastric cancers. Ppm1E expression was elevated in human gastric cancer tissues (vs. normal tissues), which was correlated with AMPK (p-AMPKα, Thr-172) dephosphorylation and mTOR complex 1 (mTORC1) activation. Ppm1E upregulation, AMPK inhibition and mTORC1 activation were also observed in human gastric cancer cell lines (AGS, HGC-27, and SNU601). Intriguingly, Ppm1E knockdown by shRNA induced AMPK activation, mTORC1 inactivation, and proliferation inhibition in AGS cells. On the other hand, forced over-expression of Ppm1E induced further AMPK inhibition and mTORC1 activation to enhance AGS cell proliferation. Remarkably, microRNA-135b-5p (“miR-135b-5p”), an anti-Ppm1E microRNA, was downregulated in both human gastric cancer tissues and cells. Reversely, miR-135b-5p exogenous expression caused Ppm1E depletion, AMPK activation, and AGC cell proliferation inhibition. Together, Ppm1E upregulation in human gastric cancer is important for cell proliferation, possible via regulating AMPK-mTOR signaling. Impact Journals LLC 2017-03-11 /pmc/articles/PMC5458207/ /pubmed/28423719 http://dx.doi.org/10.18632/oncotarget.16126 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Min-Bin
Liu, Yuan-Yuan
Cheng, Li-Bo
Lu, Jian-Wei
Zeng, Ping
Lu, Pei-Hua
AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title_full AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title_fullStr AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title_full_unstemmed AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title_short AMPKα phosphatase Ppm1E upregulation in human gastric cancer is required for cell proliferation
title_sort ampkα phosphatase ppm1e upregulation in human gastric cancer is required for cell proliferation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458207/
https://www.ncbi.nlm.nih.gov/pubmed/28423719
http://dx.doi.org/10.18632/oncotarget.16126
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