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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
journal contribution
posted on 2023-05-19, 20:24 authored by Iman AzimiIman Azimi, Bong, AH, Poo, GXH, Armitage, K, Lok, D, Roberts-Thomson, SJ, Monteith, GRStore-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.
History
Publication title
Cellular and Molecular Life SciencesVolume
75Issue
24Pagination
4525-4537ISSN
1420-682XDepartment/School
School of Pharmacy and PharmacologyPublisher
Birkhauser Verlag AgPlace of publication
Viadukstrasse 40-44, Po Box 133, Basel, Switzerland, Ch-4010Rights statement
© Springer Nature Switzerland AG 2018Repository Status
- Restricted