Warburg Effects in Cancer and Normal Proliferating Cells

Two Tales of the Same Name

Huiyan Sun, Liang Chen, Sha Cao, Yanchun Liang, Ying Xu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalGenomics, Proteomics and Bioinformatics
DOIs
StatePublished - Jan 1 2019

Fingerprint

Adenosinetriphosphate
Names
Cancer
Adenosine Triphosphate
Cells
Lactic acid
Lactic Acid
Cell
Glycolysis
Neoplasms
Cell Division
Acids
Secretion
Respiration
Tissue
Intracellular Space
Narrative
Hydrolysis
Cell Cycle
Accumulate

Keywords

  • Cancer
  • Cell proliferation
  • Fenton reaction
  • pH homeostasis
  • Warburg effect

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Computational Mathematics

Cite this

Warburg Effects in Cancer and Normal Proliferating Cells : Two Tales of the Same Name. / Sun, Huiyan; Chen, Liang; Cao, Sha; Liang, Yanchun; Xu, Ying.

In: Genomics, Proteomics and Bioinformatics, 01.01.2019.

Research output: Contribution to journalArticle

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