Open AccessPotassium and Sodium Channels and the Warburg Effect: Biophysical Regulation of Cancer Metabolism
Author(s) -
Jessica Iorio,
Giulia Petroni,
Claudia Duranti,
Elena Lastraioli
Publication year - 2019
Publication title -
bioelectricity
Language(s) - English
Resource type - Journals
eISSN - 2576-3113
pISSN - 2576-3105
DOI - 10.1089/bioe.2019.0017
Subject(s) - warburg effect , glutaminolysis , cancer cell , tumor microenvironment , glycolysis , intracellular ph , extracellular , microbiology and biotechnology , metabolism , intracellular , biology , anaerobic glycolysis , ion channel , hypoxia (environmental) , cancer , chemistry , cellular respiration , biochemistry , mitochondrion , receptor , genetics , organic chemistry , oxygen
Ion channels are progressively emerging as a novel class of membrane proteins expressed in several types of human cancers and regulating the different aspects of cancer cell behavior. The metabolism of cancer cells, usually composed by a variable proportion of respiration, glycolysis, and glutaminolysis, leads to the excessive production of acidic metabolic products. The presence of these acidic metabolites inside the cells results in intracellular acidosis, and hinders survival and proliferation. For this reason, tumor cells activate mechanisms of pH control that produce a constitutive increase in intracellular pH (pH i ) that is more acidic than the extracellular pH (pH e ). This condition forms a perfect microenvironment for metastatic progression and may be permissive for some of the acquired characteristics of tumors. Recent analyses have revealed complex interconnections between oncogenic activation, ion channels, hypoxia signaling and metabolic pathways that are dysregulated in cancer. Here, we summarize the molecular mechanisms of the Warburg effect and hypoxia and their association. Moreover, we discuss the recent findings concerning the involvement of ion channels in various aspects of the Warburg effect and hypoxia, focusing on the role of Na + and K + channels in hypoxic and metabolic reprogramming in cancer.