Ion channels in cancer: future perspectives and clinical potential

Abstract

Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca(2+) permeable channels, K(+) channels, Na(+) channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca(2+) permeable channels, K(+) channels, Na(+) channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors.

Keywords: Ca2+ channels; K+ channels; anion channels; apoptosis; cell proliferation; migration.

Figure 1.

Tentative model of channels and Na⁺/H⁺ ion exchanger in cell proliferation. ICF, intracellular fluid; ECF, extracellular fluid; Glc, glucose; Lct, lactate; Orai/STIM = Ca²⁺ release-activated Ca²⁺ channel (adapted from Lang et al. [50]). (Online version in colour.)