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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

Pharmacological Inhibition of Store-Operated Calcium Entry in MDA-MB-468 Basal A Breast Cancer Cells: Consequences on Calcium Signalling, Cell Migration and Proliferation

Iman Azimi, Alice H Bong, Greta X H Poo, Kaela Armitage, Dawn Lok, Sarah J Roberts-Thomson, Gregory R Monteith

Cell Mol Life Sci. 2018 Dec;75(24):4525-4537.

PMID: 30105615

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-specific 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 effects 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 different breast cancer basal cell line model, MDA-MB-468. The effects 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+ influx 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 differentially affected by Synta66 and YM58483. These studies highlight the need to define the exact mechanisms of action of different store-operated calcium entry inhibitors and the impact of such differences in the control of tumour progression pathways.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP835904513	Synta66		835904-51-3	Price

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