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Adenylate Kinase and Metabolic Signaling in Cancer Cells

A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ A...

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Autores principales: Klepinin, Aleksandr, Zhang, Song, Klepinina, Ljudmila, Rebane-Klemm, Egle, Terzic, Andre, Kaambre, Tuuli, Dzeja, Petras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248387/
https://www.ncbi.nlm.nih.gov/pubmed/32509571
http://dx.doi.org/10.3389/fonc.2020.00660
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author Klepinin, Aleksandr
Zhang, Song
Klepinina, Ljudmila
Rebane-Klemm, Egle
Terzic, Andre
Kaambre, Tuuli
Dzeja, Petras
author_facet Klepinin, Aleksandr
Zhang, Song
Klepinina, Ljudmila
Rebane-Klemm, Egle
Terzic, Andre
Kaambre, Tuuli
Dzeja, Petras
author_sort Klepinin, Aleksandr
collection PubMed
description A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ AMP→ AMPK signaling controlling cell cycle and proliferation, and ATP energy transfer from mitochondria to distribute energy among cellular processes. The significance of AK isoform network in the regulation of a variety of cellular processes, which include cell differentiation and motility, is rapidly growing. Adenylate kinase 2 (AK2) isoform, localized in intermembrane and intra-cristae space, is vital for mitochondria nucleotide exchange and ATP export. AK2 deficiency disrupts cell energetics, causes severe human diseases, and is embryonically lethal in mice, signifying the importance of catalyzed phosphotransfer in cellular energetics. Suppression of AK phosphotransfer and AMP generation in cancer cells and consequently signaling through AMPK could be an important factor in the initiation of cancerous transformation, unleashing uncontrolled cell cycle and growth. Evidence also builds up that shift in AK isoforms is used later by cancer cells for rewiring energy metabolism to support their high proliferation activity and tumor progression. As cell motility is an energy-consuming process, positioning of AK isoforms to increased energy consumption sites could be an essential factor to incline cancer cells to metastases. In this review, we summarize recent advances in studies of the significance of AK isoforms involved in cancer cell metabolism, metabolic signaling, metastatic potential, and a therapeutic target.
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spelling pubmed-72483872020-06-05 Adenylate Kinase and Metabolic Signaling in Cancer Cells Klepinin, Aleksandr Zhang, Song Klepinina, Ljudmila Rebane-Klemm, Egle Terzic, Andre Kaambre, Tuuli Dzeja, Petras Front Oncol Oncology A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ AMP→ AMPK signaling controlling cell cycle and proliferation, and ATP energy transfer from mitochondria to distribute energy among cellular processes. The significance of AK isoform network in the regulation of a variety of cellular processes, which include cell differentiation and motility, is rapidly growing. Adenylate kinase 2 (AK2) isoform, localized in intermembrane and intra-cristae space, is vital for mitochondria nucleotide exchange and ATP export. AK2 deficiency disrupts cell energetics, causes severe human diseases, and is embryonically lethal in mice, signifying the importance of catalyzed phosphotransfer in cellular energetics. Suppression of AK phosphotransfer and AMP generation in cancer cells and consequently signaling through AMPK could be an important factor in the initiation of cancerous transformation, unleashing uncontrolled cell cycle and growth. Evidence also builds up that shift in AK isoforms is used later by cancer cells for rewiring energy metabolism to support their high proliferation activity and tumor progression. As cell motility is an energy-consuming process, positioning of AK isoforms to increased energy consumption sites could be an essential factor to incline cancer cells to metastases. In this review, we summarize recent advances in studies of the significance of AK isoforms involved in cancer cell metabolism, metabolic signaling, metastatic potential, and a therapeutic target. Frontiers Media S.A. 2020-05-19 /pmc/articles/PMC7248387/ /pubmed/32509571 http://dx.doi.org/10.3389/fonc.2020.00660 Text en Copyright © 2020 Klepinin, Zhang, Klepinina, Rebane-Klemm, Terzic, Kaambre and Dzeja. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Klepinin, Aleksandr
Zhang, Song
Klepinina, Ljudmila
Rebane-Klemm, Egle
Terzic, Andre
Kaambre, Tuuli
Dzeja, Petras
Adenylate Kinase and Metabolic Signaling in Cancer Cells
title Adenylate Kinase and Metabolic Signaling in Cancer Cells
title_full Adenylate Kinase and Metabolic Signaling in Cancer Cells
title_fullStr Adenylate Kinase and Metabolic Signaling in Cancer Cells
title_full_unstemmed Adenylate Kinase and Metabolic Signaling in Cancer Cells
title_short Adenylate Kinase and Metabolic Signaling in Cancer Cells
title_sort adenylate kinase and metabolic signaling in cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248387/
https://www.ncbi.nlm.nih.gov/pubmed/32509571
http://dx.doi.org/10.3389/fonc.2020.00660
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