Thus aberrant channels' expression and/or function can impair these processes driving the transformation of normal cells into malignant derivatives that exhibit uncontrolled multiplication and spreading, which are hallmarks of cancer ( 201). Among these processes also are those that are crucial for maintaining normal tissue homeostasis, such as cell proliferation, migration, and apoptosis. Redistribution of ions among cellular compartments as a result of channels' opening can affect a plethora of cellular processes and functions ranging from electrical excitation to locomotion. Ion channels are integral membrane proteins that contain an aqueous pore through which, when it is open, certain ions can move freely between these compartments ( 208). Various ion species are asymmetrically distributed between extracellular and intracellular milieu as well as among various lipid membrane-confined cellular compartments. In this review the authors provide arguments to substantiate such point of view. Although the relation of cancer hallmarks to ion channel dysfunction differs from classical definition of channelopathies, as disease states causally linked with inherited mutations of ion channel genes that alter channel's biophysical properties, in a broader context of the disease state, to which pathogenesis ion channels essentially contribute, such classification seems absolutely appropriate. Moreover, tight association of these hallmarks with ion channel dysfunction gives a good reason to classify them as special type of channelopathies, namely oncochannelopathies. Membrane proteins responsible for signaling within cell and among cells, for coupling of extracellular events with intracellular responses, and for maintaining intracellular ionic homeostasis ion channels contribute to various extents to pathophysiological features of each cancer hallmark. Among the genes affected by cancer, those encoding ion channels are present. Although nowadays the catalog of cancer hallmarks is quite broad, the most common and obvious of them are 1) uncontrolled proliferation, 2) resistance to programmed cell death (apoptosis), 3) tissue invasion and metastasis, and 4) sustained angiogenesis. However, all cancer cell genotypes generally translate into several common pathophysiological features, often referred to as cancer hallmarks. Genomic instability is a primary cause and fundamental feature of human cancer.
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