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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, GR
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.

History

Publication title

Cellular and Molecular Life Sciences

Volume

75

Issue

24

Pagination

4525-4537

ISSN

1420-682X

Department/School

School of Pharmacy and Pharmacology

Publisher

Birkhauser Verlag Ag

Place of publication

Viadukstrasse 40-44, Po Box 133, Basel, Switzerland, Ch-4010

Rights statement

© Springer Nature Switzerland AG 2018

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the biological sciences

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