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Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A breast cancer cells: consequences on calcium signalling, cell migration and proliferation

Azimi, I ORCID: 0000-0001-9477-9999, Bong, AH, Poo, GXH, Armitage, K, Lok, D, Roberts-Thomson, SJ and Monteith, GR 2018 , 'Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A breast cancer cells: consequences on calcium signalling, cell migration and proliferation' , Cellular and Molecular Life Sciences, vol. 75, no. 24 , pp. 4525-4537 , doi: 10.1007/s00018-018-2904-y.

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Abstract

Store-operated Ca2+ entry is a pathway that is remodelled in a variety of cancers, and altered expression of the components of store-operated Ca2+ entry is a feature of breast cancer cells of the basal molecular subtype. Studies of store-operated Ca2+ entry in breast cancer cells have used non-specifc pharmacological inhibitors, complete depletion of intracellular Ca2+ stores and have mostly focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies compared the efects of the selective store-operated Ca2+ entry inhibitors Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca2+ ([Ca2+]CYT) changes induced by physiological stimuli in a diferent breast cancer basal cell line model, MDA-MB-468. The efects of these agents on proliferation as well as serum and epidermal growth factor (EGF) induced migration were also assessed. Activation with the purinergic receptor activator adenosine triphosphate, produced a sustained increase in [Ca2+]CYT that was entirely dependent on store-operated Ca2+ entry. The protease activated receptor 2 activator, trypsin, and EGF also produced Ca2+ infux that was sensitive to both Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells was sensitive to both store-operated Ca2+ inhibitors. However, proliferation and EGF-activated migration was diferentially afected by Synta66 and YM58483. These studies highlight the need to defne the exact mechanisms of action of diferent store-operated calcium entry inhibitors and the impact of such diferences in the control of tumour progression pathways.

Item Type: Article
Authors/Creators:Azimi, I and Bong, AH and Poo, GXH and Armitage, K and Lok, D and Roberts-Thomson, SJ and Monteith, GR
Keywords: pharmacology, cancer, Orai1, store-operated calcium entry, Synta66, YM58483
Journal or Publication Title: Cellular and Molecular Life Sciences
Publisher: Birkhauser Verlag Ag
ISSN: 1420-682X
DOI / ID Number: 10.1007/s00018-018-2904-y
Copyright Information:

© Springer Nature Switzerland AG 2018

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