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.

Downregulation of Ca2+-Activated Cl− Channel TMEM16A by the Inhibition of Histone Deacetylase in TMEM16A-Expressing Cancer Cells

“…In cancer cells, ion channels regulate cell proliferation and apoptosis via the modulation of membrane potential and intracellular Ca 21 -mobilization (Yang and Brackenbury, 2013;Lang and Stournaras, 2014;Pardo and Stühmer, 2014) and thus are both potential therapeutic targets and biomarkers for cancer. Histone acetylation and DNA methylation on gene expression play important roles in various cellular processes such as proliferation, differentiation, and apoptosis, and DNA methylation is a key regulator of the transient receptor potential Ca 21 channel TRPC3 and inward-rectifier K 1 channel K ir 4.1 (Martin-Trujillo et al, 2011;Nwaobi et al, 2014).…”

“…Ion channels contribute to a variety of cancer processes, such as proliferation, apoptosis, migration, and invasion, via regulation of the resting membrane potential and intracellular Ca 21 signaling (Yang and Brackenbury, 2013;Lang and Stournaras, 2014;Pardo and Stühmer, 2014). Pharmacologic blockade of ion channels is an attractive target to both suppress tumor growth and prevent tumor metastasis.…”

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

“…Other calcium channels, such as the calcium channelassociated TRP, provide Ca 21 entry pathways and modulate the driving force for calcium entry (Lang and Stournaras, 2014). These channels have continuously emerged as important factors in several highly prevalent pathologies, cancer included (Holzer and Izzo, 2014), which increases the potential of TRP therapies.…”

“…Distinct classes of Ca 21 -permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth (Lang and Stournaras, 2014 (Leanza et al, 2016). Moreover, a wide variety of distinct Ca 21 -permeable channels, such as TRP channels, have been linked to tumor proliferation and metastasis (Lang and Stournaras, 2014). Experimental modification of TRP channels activity impacts tumor cell function and motility, which suggests that the channels are a potential molecular target for tumor neovascularization control (Fiorio Pla et al, 2012).…”

“…Several studies have revealed that voltagegated ion channels can contribute significantly to cell mitotic biochemical signaling, cell cycle progression, and cell volume regulation, processes that are critical for cancer cell proliferation (Rao et al, 2015). Distinct classes of Ca 21 -permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth (Lang and Stournaras, 2014 (Leanza et al, 2016). Moreover, a wide variety of distinct Ca 21 -permeable channels, such as TRP channels, have been linked to tumor proliferation and metastasis (Lang and Stournaras, 2014).…”