The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela

CARDONE, Rosa, ALFAROUK, Khalid, ELLIOTT, Robert, ALQAHTANI, Saad, AHMED, Samrein, ALJARBOU, Ahmed, GRECO, Maria, CANNONE, Stefania and RESHKIN, Stephan (2019). The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela. International Journal of Molecular Sciences, 20 (15): 3694.

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Official URL: https://www.mdpi.com/1422-0067/20/15/3694
Link to published version:: https://doi.org/10.3390/ijms20153694

Abstract

Cancer cells have an unusual regulation of hydrogen ion dynamics that are driven by poor vascularity perfusion, regional hypoxia, and increased glycolysis. All these forces synergize/orchestrate together to create extracellular acidity and intracellular alkalinity. Precisely, they lead to extracellular pH (pHe) values as low as 6.2 and intracellular pH values as high as 8. This unique pH gradient (∆pHi to ∆pHe) across the cell membrane increases as the tumor progresses, and is markedly displaced from the electrochemical equilibrium of protons. These unusual pH dynamics influence cancer cell biology, including proliferation, metastasis, and metabolic adaptation. Warburg metabolism with increased glycolysis, even in the presence of Oxygen with the subsequent reduction in Krebs’ cycle, is a common feature of most cancers. This metabolic reprogramming confers evolutionary advantages to cancer cells by enhancing their resistance to hypoxia, to chemotherapy or radiotherapy, allowing rapid production of biological building blocks that support cellular proliferation, and shielding against damaging mitochondrial free radicals. In this article, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression, adaptation, and in determining the programming and re-programming of tumor cell metabolism.

Item Type: Article
Uncontrolled Keywords: 0399 Other Chemical Sciences; 0604 Genetics; 0699 Other Biological Sciences; Chemical Physics; 3101 Biochemistry and cell biology; 3107 Microbiology; 3404 Medicinal and biomolecular chemistry
Identification Number: https://doi.org/10.3390/ijms20153694
SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 31 Jan 2024 15:56
Last Modified: 31 Jan 2024 16:00
URI: https://shura.shu.ac.uk/id/eprint/33080

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