Abstract
Plasma membrane ion channels contribute to virtually all basic cellular processes, including such crucial ones for maintaining tissue homeostasis as proliferation, differentiation, and apoptosis. Enhanced proliferation, aberrant differentiation, and impaired ability to die are the prime reasons for abnormal tissue growth, which can eventually turn into uncontrolled expansion and invasion, characteristic of cancer. Prostate cancer (PCa) cells express a variety of plasma membrane ion channels. By providing the influx of essential signaling ions, perturbing intracellular ion concentrations, regulating cell volume, and maintaining membrane potential, PCa cells are critically involved in proliferation, differentiation, and apoptosis. PCa cells of varying metastatic ability can be distinguished by their ion channel characteristics. Increased malignancy and invasiveness of androgen-independent PCa cells is generally associated with the shift to a ‘more excitable’ phenotype of their plasma membrane. This shift is manifested by the appearance of voltage-gated Na+ and Ca2+ channels which contribute to their enhanced apoptotic resistance together with downregulated store-operated Ca2+ influx, altered expression of different K+ channels and members of the Transient Receptor Potential (TRP) channel family, and strengthened capability for maintaining volume constancy. The present review examines channel types expressed by PCa cells and their involvement in metastatic behaviors.
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Abbreviations
- AR:
-
androgen receptor
- AVD:
-
apoptotic volume decrease
- [Ca2+]in:
-
intracellular Ca2+ concentration
- CRAC:
-
Ca2+ release-activated channel
- DAG:
-
diacylglycerol
- ER:
-
endoplasmic reticulum
- ICl,swell:
-
swelling-activated Cl− current
- IDAG:
-
current through DAG-gated cationic channels
- IK:
-
K+ current
- Imenthol:
-
menthol-activated current through cold/menthol-sensitive TRPM8
- IP3:
-
inositol trisphosphate
- ISOC:
-
store-operated membrane current
- LVA:
-
low voltage-activated
- NE:
-
neuroendocrine
- PCa:
-
prostate cancer
- PLC:
-
phospholipase C
- RVD:
-
regulatory volume decrease
- SOC:
-
store-operated channel
- SOCE:
-
store-operated calcium entry
- TEA:
-
tetraethylammonium
- TTX:
-
tetrodotoxin
- VGCC, voltage-gated Ca2+ channel, VGSC:
-
voltage-gated sodium channel
- VRAC:
-
volume-regulated anion channel
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Acknowledgements
This work was supported by grants from INSERM, the French Minsistry of Education, La Ligue Nationale Contre le Cancer, the Nord/Pas-de-Calais region, and INTAS 05-1000008-8223.
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Prevarskaya, N., Skryma, R., Bidaux, G. et al. Ion channels in death and differentiation of prostate cancer cells. Cell Death Differ 14, 1295–1304 (2007). https://doi.org/10.1038/sj.cdd.4402162
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DOI: https://doi.org/10.1038/sj.cdd.4402162
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