The role of ion channels and transporters in cell proliferation and cancer

After the early wavering steps tracing back to at least the 1960's (Cone, 1974;Binggeli and Cameron, 1980), the study of ion transport in cell proliferation and neoplasia is on its way to become a mature research field (Arcangeli et al., 2009).Wide evidence is now available about the regulatory roles exerted by ion channels and transporters on the cell cycle phases (Becchetti, 2011) and other aspects of cell physiology that shape the multistep neoplastic progression, such as resistance to apoptosis (Lehen'kyi et al., 2011), cell invasiveness (Becchetti andArcangeli, 2010), and angiogenesis (Fiorio Pla et al., 2012).Ion transport is implicated in these cell functions in many ways, from the classic mechanisms relating membrane potential (V m ) to Ca 2+ homeostasis, to the control of pH, cell volume, growth factor release, interaction with the extracellular matrix, and so forth.Some of these actions probably occur through non-conductive mechanisms, such as intrinsic enzyme activity or conformational coupling with other membrane proteins (e.g., Arcangeli and Becchetti, 2006;Hegle et al., 2006).A major function of ion channels is to mediate the cell interaction with its environment.In the case of cancer cells, the interaction with the tumor milieu' has relevant implications for therapy (Arcangeli, 2011).The Research Topic Issue on Ion Transport in Cell Cycle and Cancer addresses classic issues in the field as well as it points to novel perspectives.One example of the latter is the role of Ca 2+ in autophagy (Rizzuto et al., 2012), which has not received as much attention as Ca 2+ signaling in the cell cycle machinery and apoptosis (Roderick and Cook, 2008;Munaron, 2012).As discussed by Kondratskyi et al. (2013), modulating autophagy has a great potential in cancer diagnosis and treatment.The review discusses the related Ca 2+ -dependent mechanisms and their meaning in the context of cancer progression and therapy.The role of Ca 2+ in autophagy is related to the increasing recognition of the multiple functions of intracellular ion channels, which regulate ion transport across the membranes of cellular organelles.Leanza et al. (2013) provide an updated overview of the role of ion channels in mitochondria, endoplasmic reticulum, nucleus, endosomes, and lysosomes, with special attention to the implications for the biology of cancer.A general picture of the role of V m in cell proliferation and differentiation is provided by Yang and Brackenbury (2013), with a special focus on voltage-gated channels.The paper reviews what is known about the V m changes during cell cycle and the implications of different types of ion channels in the cell cycle stages, www.frontiersin.org