Apr 19, 2020

The Na+/K+ ATPase Regulates Glycolysis and Defines Immunometabolism in Tumors

BioRxiv : the Preprint Server for Biology
David M RockeJason W. Locasale


Cancer therapies targeting metabolism have been limited due to a lack of understanding of the controlling properties of vulnerable pathways. The Na+/K+ ATPase is responsible for a large portion of cellular energy demands but how these demands influence metabolism and create metabolic liabilities are not known. Using metabolomic approaches, we first show that digoxin, a cardiac glycoside widely used in humans, acts through disruption to central carbon metabolism via on target inhibition of the Na+/K+ ATPase that was fully recovered by expression of an allele resistant to digoxin. We further show in vivo that administration of digoxin inhibits glycolysis in both malignant and healthy cells, particularly within clinically relevant cardiac tissue, while exhibiting tumor-specific cytotoxic activity in an allografted soft tissue sarcoma. Single-cell expression analysis of over 31,000 cells within the sarcoma shows that acute Na+/K+ ATPase inhibition shifts the immune composition of the tumor microenvironment, leading to selective transcriptional reprogramming of metabolic processes in specific immune cells thus acting both through tumor cell autonomous and non-autonomous (e.g. macrophage) cells. These results provide evidence that al...Continue Reading

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Sequence Determinations, RNA
Gene Expression Analysis

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

The Australian Nurses' Journal
K C Lee
British Journal of Hospital Medicine
J R Hampton
Prescrire International
Soins. Cardiologie
R Niddam, M Perrot-Marsault
Journal of the American Pharmaceutical Association
© 2020 Meta ULC. All rights reserved