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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

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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-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.

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Abbreviations

ATP:

Adenosine triphosphate

CM:

Complete media

CPA:

Cyclopiazonic acid

DMEM:

Dulbecco’s modified Eagle’s medium

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

ER:

Endoplasmic reticulum

FBS:

Foetal bovine serum

IP3 :

Inositol 1,4,5-trisphosphate

PAR2:

Protease-activated receptor 2

PBS:

Phosphate-buffered saline

PLC:

Phospholipase C

SOCE:

Store-operated Ca2+ entry

SRM:

Serum-reduced media

STIM1:

Stromal interaction molecule 1

STR:

Short tandem repeat

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Acknowledgements

This research was partially supported by the National Health and Medical Research Council (NHMRC; project Grant 1079672). G.R.M. is supported by the Mater Foundation. The Translational Research Institute is supported by a Grant from the Australian Government.

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Authors and Affiliations

  1. School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia

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

  2. Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia

    Iman Azimi & Gregory R. Monteith

  3. Division of Pharmacy, College of Health and Medicine, University of Tasmania, Hobart, TAS, Australia

    Iman Azimi

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  1. Iman Azimi
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  2. Alice H. Bong
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Correspondence to Gregory R. Monteith.

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GR.M. and S.J.R.-T. are associated with QUE Oncology Inc.

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Azimi, I., Bong, A.H., Poo, G.X.H. et al. Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A breast cancer cells: consequences on calcium signalling, cell migration and proliferation. Cell. Mol. Life Sci. 75, 4525–4537 (2018). https://doi.org/10.1007/s00018-018-2904-y

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