TY - JOUR

T1 - pH gradient reversal fuels cancer progression

AU - Zheng, Tianyu

AU - Jäättelä, Marja

AU - Liu, Bin

PY - 2020

Y1 - 2020

N2 - pH gradient reversal refers to intracellular alkalization and extracellular acidification commonly seen in malignant tumors. To meet their high anabolic demand, cancer cells rewire their glucose metabolism from oxidative phosphorylation to lactate fermentation, which results in the excessive generation of protons. To avoid lethal cytosolic acidification, lactate-fermenting cancer cells activate multiple acid removal pathways leading to the acidification of the extracellular space. This acidification is often further intensified by the defective capacity of the disorganized tumor vasculature to dilute protons away from the cancer tissue. The cancer-specific proton equilibrium with highly alkaline cytosol and acidic extracellular space is emerging as a fundamental driving force for cancer growth. Here, we discuss how cancer cells establish and maintain reversed pH gradient, how pH gradient reversal fuels cancer progression, and how these mechanisms can be targeted in cancer therapy.

AB - pH gradient reversal refers to intracellular alkalization and extracellular acidification commonly seen in malignant tumors. To meet their high anabolic demand, cancer cells rewire their glucose metabolism from oxidative phosphorylation to lactate fermentation, which results in the excessive generation of protons. To avoid lethal cytosolic acidification, lactate-fermenting cancer cells activate multiple acid removal pathways leading to the acidification of the extracellular space. This acidification is often further intensified by the defective capacity of the disorganized tumor vasculature to dilute protons away from the cancer tissue. The cancer-specific proton equilibrium with highly alkaline cytosol and acidic extracellular space is emerging as a fundamental driving force for cancer growth. Here, we discuss how cancer cells establish and maintain reversed pH gradient, how pH gradient reversal fuels cancer progression, and how these mechanisms can be targeted in cancer therapy.

KW - Cancer

KW - Cell biology

KW - Glycolysis

KW - Lysosome

KW - pH gradient reversal

U2 - 10.1016/j.biocel.2020.105796

DO - 10.1016/j.biocel.2020.105796

M3 - Review

C2 - 32593663

AN - SCOPUS:85087393984

VL - 125

JO - International Journal of Biochemistry & Cell Biology

JF - International Journal of Biochemistry & Cell Biology

SN - 1357-2725

M1 - 105796

ER -