Constitutive calcium entry and cancer: updated views and insights

Eur Biophys J. 2017 Jul;46(5):395-413. doi: 10.1007/s00249-017-1216-8. Epub 2017 May 17.

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.

Keywords: Cancer; Constitutive/basal Ca2+ entry; Orai; SPCA; STIM; TRP.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology

Substances

  • Calcium