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

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.

Keywords: chloride channels; chloride-associated transporters; metastasis; migration and invasion; prognostic marker.

Figure 1

Schema of chloride channel-associated cancers. Chloride channels are involved in at least two types of cancers. Identification of shared chloride channels might provide clues to identify metastatic cancer. VDAC1: Voltage-dependent anion channel 1, TMEM: Transmembrane member, CLC: Voltage-gated chloride channels, CLIC: Chloride intracellular channels, CFTR: Cystic fibrosis transmembrane conductance regulator.