Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers

SIMPLE SUMMARY: Roles of chloride-associated transporters have been raised in various cancers. Although complicated ion movements, crosstalk among channels/transporters through homeostatic electric regulation, difficulties with experimental implementation such as activity measurement of intracellular location were disturbed to verify the precise modulation of channels/transporters, recently defined cancerous function and communication with tumor microenvironment of chloride channels/transporters should be highlighted beyond classical homeostatic ion balance. Chloride-associated transporters as membrane-associated components of chloride movement, regulations of transmembrane member 16A, calcium-activated chloride channel regulators, transmembrane member 206, chloride intracellular channels, voltage-gated chloride channels, cystic fibrosis transmembrane conductance regulator, voltage-dependent anion channel, volume-regulated anion channel, and chloride-bicarbonate exchangers are discussed. ABSTRACT: The canonical roles of chloride channels and chloride-associated transporters have been physiologically determined; these roles include the maintenance of membrane potential, pH balance, and volume regulation and subsequent cellular functions such as autophagy and cellular proliferative processes. However, chloride channels/transporters also play other roles, beyond these classical function, in cancerous tissues and under specific conditions. Here, we focused on the chloride channel-associated cancers and present recent advances in understanding the environments of various types of cancer caused by the participation of many chloride channel or transporters families and discuss the challenges and potential targets for cancer treatment. The modulation of chloride channels/transporters might promote new aspect of cancer treatment strategies.