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Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name

It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer...

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Autores principales: Sun, Huiyan, Chen, Liang, Cao, Sha, Liang, Yanchun, Xu, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818181/
https://www.ncbi.nlm.nih.gov/pubmed/31071451
http://dx.doi.org/10.1016/j.gpb.2018.12.006
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author Sun, Huiyan
Chen, Liang
Cao, Sha
Liang, Yanchun
Xu, Ying
author_facet Sun, Huiyan
Chen, Liang
Cao, Sha
Liang, Yanchun
Xu, Ying
author_sort Sun, Huiyan
collection PubMed
description It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.
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spelling pubmed-68181812019-11-01 Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name Sun, Huiyan Chen, Liang Cao, Sha Liang, Yanchun Xu, Ying Genomics Proteomics Bioinformatics Original Research It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons. Elsevier 2019-06 2019-05-07 /pmc/articles/PMC6818181/ /pubmed/31071451 http://dx.doi.org/10.1016/j.gpb.2018.12.006 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research
Sun, Huiyan
Chen, Liang
Cao, Sha
Liang, Yanchun
Xu, Ying
Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title_full Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title_fullStr Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title_full_unstemmed Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title_short Warburg Effects in Cancer and Normal Proliferating Cells: Two Tales of the Same Name
title_sort warburg effects in cancer and normal proliferating cells: two tales of the same name
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818181/
https://www.ncbi.nlm.nih.gov/pubmed/31071451
http://dx.doi.org/10.1016/j.gpb.2018.12.006
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