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Constitutive calcium entry and cancer: updated views and insights

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Abstract

Tight control of basal cytosolic Ca2+ concentration is essential for cell survival and to fine-tune Ca2+-dependent cell functions. A way to control this basal cytosolic Ca2+ concentration is to regulate membrane Ca2+ channels including store-operated Ca2+ channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca2+ channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca2+ channels contributes to Ca2+ entry and the transient increase in cytosolic Ca2+ concentration involved in intracellular signaling. However, in various experimental conditions, Ca2+ entry and/or Ca2+ currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca2+ channels are already open/activated in basal condition, contributing therefore to constitutive Ca2+ entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.

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Freely adapted from Saul et al. (2014)

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Abbreviations

ARC:

Arachidonate-regulated Ca2+

BKCa:

Big-conductance Ca2+-activated K+ channels

B-SOCE:

Basal store-operated calcium entry

CaV3.2:

Voltage-gated Ca2+ channel 3.2

CRAC:

Ca2+ release-activated Ca2+

GPCR:

G-protein-coupled receptor

hEAG1:

Human ether à go-go K+ channel 1

IKCa:

Intermediate conductance Ca2+-activated K+ channels

LPA:

Lysophosphatidic acid

LPC:

Lysophosphatidylcholine

NVG-Ca2+ channel:

Non-voltage-gated Ca2+ channel

P2X:

Purinergic ionotropic receptor

R-SOCE:

Receptor-triggered store-operated Ca2+ entry influx

SPCA:

Secretory pathway Ca2+-ATPase

SKCa:

Small-conductance Ca2+-activated K+ channels

SMOC:

Secondary messenger-operated channels

STIM:

Stromal interaction molecule

SAC:

Stretch-activated channels

SOC:

Store-operated channels

TRPC:

Transient receptor potential canonical

TRPM7:

Transient receptor potential melastatin-related 7

TRPV:

Transient receptor potential vanilloid

VOCC:

Voltage-operated calcium channels

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Acknowledgements

This work was supported by la Ligue Contre le Cancer (comités des régions Bretagne, Pays de la Loire, Centre, and Poitou-Charentes), Region Centre (LIPIDS project of ARD2020-Biomédicaments), Inserm, CNRS, Cancéropôle Grand Ouest, the association “CANCEN”, Tours’ Hospital oncology association ACORT, Fondation ARC, ANR (ANR-12-JSV2-0004-001), Biosit, University of Brest, University of Rennes 1, University of Poitiers, University of Tours, and Roche-SFD.

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Special Issue: Ion Channels, Transporters, and Cancer.

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Mignen, O., Constantin, B., Potier-Cartereau, M. et al. Constitutive calcium entry and cancer: updated views and insights. Eur Biophys J 46, 395–413 (2017). https://doi.org/10.1007/s00249-017-1216-8

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