scholarly journals The Golgi as a “Proton Sink” in Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Koen M. O. Galenkamp ◽  
Cosimo Commisso
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Cancer Cells ◽  
Atp Hydrolysis ◽  
Membrane Transporters ◽  
Glycolytic Flux ◽  
Proton Channels ◽  
Optimal Functioning ◽  
Dependent Processes

Cancer cells exhibit increased glycolytic flux and adenosine triphosphate (ATP) hydrolysis. These processes increase the acidic burden on the cells through the production of lactate and protons. Nonetheless, cancer cells can maintain an alkaline intracellular pH (pHi) relative to untransformed cells, which sets the stage for optimal functioning of glycolytic enzymes, evasion of cell death, and increased proliferation and motility. Upregulation of plasma membrane transporters allows for H+ and lactate efflux; however, recent evidence suggests that the acidification of organelles can contribute to maintenance of an alkaline cytosol in cancer cells by siphoning off protons, thereby supporting tumor growth. The Golgi is such an acidic organelle, with resting pH ranging from 6.0 to 6.7. Here, we posit that the Golgi represents a “proton sink” in cancer and delineate the proton channels involved in Golgi acidification and the ion channels that influence this process. Furthermore, we discuss ion channel regulators that can affect Golgi pH and Golgi-dependent processes that may contribute to pHi homeostasis in cancer.

scholarly journals Plasma membrane ion channels and epithelial to mesenchymal transition in cancer cells

2016 ◽  
Vol 23 (11) ◽  
pp. R517-R525 ◽  
Author(s):  
Iman Azimi ◽  
Gregory R Monteith
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Ion Channel ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Resistance ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Pharmacological Modulation ◽  
Channel Expression

A variety of studies have suggested that epithelial to mesenchymal transition (EMT) may be important in the progression of cancer in patients through metastasis and/or therapeutic resistance. A number of pathways have been investigated in EMT in cancer cells. Recently, changes in plasma membrane ion channel expression as a consequence of EMT have been reported. Other studies have identified specific ion channels able to regulate aspects of EMT induction. The utility of plasma membrane ion channels as targets for pharmacological modulation make them attractive for therapeutic approaches to target EMT. In this review, we provide an overview of some of the key plasma membrane ion channel types and highlight some of the studies that are beginning to define changes in plasma membrane ion channels as a consequence of EMT and also their possible roles in EMT induction.

scholarly journals Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Florian Ullrich ◽  
Sandy Blin ◽  
Katina Lazarow ◽  
Tony Daubitz ◽  
Jens Peter von Kries ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Gene Family ◽  
Chloride Channels ◽  
Anion Channel ◽  
Ion Permeation ◽  
Acid Sensing Ion Channels ◽  
Genome Wide ◽  
A Genome

Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated chloride channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying anion channel PAORAC/ASOR. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.

scholarly journals Identification of TMEM206 proteins as pore of ASOR acid-sensitive chloride channels

2019 ◽  
Author(s):  
Florian Ullrich ◽  
Sandy Blin ◽  
Katina Lazarow ◽  
Tony Daubitz ◽  
Jens-Peter von Kries ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Ion Permeation ◽  
Anion Channels ◽  
Acid Sensing Ion Channels ◽  
Genome Wide ◽  
A Genome

ABSTRACTAcid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated anion channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying ASOR chloride channel. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.

Ion channnels and transporters in cancer. 5. Ion channels in control of cancer and cell apoptosis

2011 ◽  
Vol 301 (6) ◽  
pp. C1281-C1289 ◽  
Author(s):  
V'yacheslav Lehen'kyi ◽  
George Shapovalov ◽  
Roman Skryma ◽  
Natalia Prevarskaya
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Programmed Cell Death ◽  
Tissue Homeostasis ◽  
Death Rates ◽  
Cellular Processes ◽  
Regulation Of Cell Cycle

Ion channels contribute to virtually all basic cellular processes, including such crucial ones for maintaining tissue homeostasis as proliferation, differentiation, and apoptosis. The involvement of ion channels in regulation of programmed cell death, or apoptosis, has been known for at least three decades based on observation that classical blockers of ion channels can influence cell death rates, prolonging or shortening cell survival. Identification of the central role of these channels in regulation of cell cycle and apoptosis as well as the recent discovery that the expression of ion channels is not limited solely to the plasma membrane, but may also include membranes of internal compartments, has led researchers to appreciate the pivotal role of ion channels plays in development of cancer. This review focuses on the aspects of programmed cell death influenced by various ion channels and how dysfunctions and misregulations of these channels may affect the development and progression of different cancers.

Plasma membrane ion channels in suicidal cell death

2007 ◽  
Vol 462 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Florian Lang ◽  
Stephan M. Huber ◽  
Ildiko Szabo ◽  
Erich Gulbins
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels

scholarly journals Plasma Membrane Transporters as Biomarkers and Molecular Targets in Cholangiocarcinoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 498
Author(s):  
Jose J.G. Marin ◽  
Rocio I.R. Macias ◽  
Candela Cives-Losada ◽  
Ana Peleteiro-Vigil ◽  
Elisa Herraez ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cancer Cells ◽  
Antitumor Agents ◽  
Essential Element ◽  
Chemotherapeutic Agents ◽  
Membrane Transporters ◽  
Drug Uptake ◽  
Abc Proteins ◽  
Dismal Prognosis ◽  
Intracellular Targets

The dismal prognosis of patients with advanced cholangiocarcinoma (CCA) is due, in part, to the extreme resistance of this type of liver cancer to available chemotherapeutic agents. Among the complex mechanisms accounting for CCA chemoresistance are those involving the impairment of drug uptake, which mainly occurs through transporters of the superfamily of solute carrier (SLC) proteins, and the active export of drugs from cancer cells, mainly through members of families B, C and G of ATP-binding cassette (ABC) proteins. Both mechanisms result in decreased amounts of active drugs able to reach their intracellular targets. Therefore, the “cancer transportome”, defined as the set of transporters expressed at a given moment in the tumor, is an essential element for defining the multidrug resistance (MDR) phenotype of cancer cells. For this reason, during the last two decades, plasma membrane transporters have been envisaged as targets for the development of strategies aimed at sensitizing cancer cells to chemotherapy, either by increasing the uptake or reducing the export of antitumor agents by modulating the expression/function of SLC and ABC proteins, respectively. Moreover, since some elements of the transportome are differentially expressed in CCA, their usefulness as biomarkers with diagnostic and prognostic purposes in CCA patients has been evaluated.

scholarly journals Scorpion Toxins and Ion Channels: Potential Applications in Cancer Therapy

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 326
Author(s):  
Rosa Amalia Dueñas-Cuellar ◽  
Carlos José Correia Santana ◽  
Ana Carolina Martins Magalhães ◽  
Osmindo Rodrigues Pires ◽  
Wagner Fontes ◽  
...  
Keyword(s):  
Cell Death ◽  
Ion Channels ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Scorpion Toxins ◽  
Inhibitory Effects ◽  
Death Rates ◽  
Potential Applications ◽  
Biochemical Mechanisms ◽  
Carcinogenic Process

Apoptosis, a genetically directed process of cell death, has been studied for many years, and the biochemical mechanisms that surround it are well known and described. There are at least three pathways by which apoptosis occurs, and each pathway depends on extra or intracellular processes for activation. Apoptosis is a vital process, but disturbances in proliferation and cell death rates can lead to the development of diseases like cancer. Several compounds, isolated from scorpion venoms, exhibit inhibitory effects on different cancer cells. Indeed, some of these compounds can differentiate between healthy and cancer cells within the same tissue. During the carcinogenic process, morphological, biochemical, and biological changes occur that enable these compounds to modulate cancer but not healthy cells. This review highlights cancer cell features that enable modulation by scorpion neurotoxins. The properties of the isolated scorpion neurotoxins in cancer cells and the potential uses of these compounds as alternative treatments for cancer are discussed.

scholarly journals Ion channels and apoptosis in cancer

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130104 ◽  
Author(s):  
Carl D. Bortner ◽  
John A. Cidlowski
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Ion Channels ◽  
Cell Growth ◽  
Cancer Cells ◽  
Critical Role ◽  
Cell Number ◽  
Tumour Formation ◽  
Constant Cell ◽  
Critical Components

Humans maintain a constant cell number throughout their lifespan. This equilibrium of cell number is accomplished when cell proliferation and cell death are kept balanced, achieving a steady-state cell number. Abnormalities in cell growth or cell death can lead to an overabundance of cells known as neoplasm or tumours. While the perception of cancer is often that of an uncontrollable rate of cell growth or increased proliferation, a decrease in cell death can also lead to tumour formation. Most cells when detached from their normal tissue die. However, cancer cells evade cell death, tipping the balance to an overabundance of cell number. Therefore, overcoming this resistance to cell death is a decisive factor in the treatment of cancer. Ion channels play a critical role in cancer in regards to cell proliferation, malignant angiogenesis, migration and metastasis. Additionally, ion channels are also known to be critical components of apoptosis. In this review, we discuss the modes of cell death focusing on the ability of cancer cells to evade apoptosis. Specifically, we focus on the role ion channels play in controlling and regulating life/death decisions and how they can be used to overcome resistance to apoptosis in the treatment of cancer.

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