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

被引:33
作者
Azimi, Iman [1 ,2 ,3 ]
Bong, Alice H. [1 ]
Poo, Greta X. H. [1 ]
Armitage, Kaela [1 ]
Lok, Dawn [1 ]
Roberts-Thomson, Sarah J. [1 ]
Monteith, Gregory R. [1 ,2 ]
机构
[1] Univ Queensland, Sch Pharm, Brisbane, Qld, Australia
[2] Univ Queensland, Mater Res Inst, Translat Res Inst, Brisbane, Qld, Australia
[3] Univ Tasmania, Div Pharm, Coll Hlth & Med, Hobart, Tas, Australia
基金
英国医学研究理事会;
关键词
Breast cancer; Orai1; Store-operated Ca2+ entry; Synta66; YM58483; EPITHELIAL-MESENCHYMAL TRANSITION; ACTIVATED CA2+ CHANNELS; CYTOKINE PRODUCTION; ORAI1; RECEPTOR; EXPRESSION; STIM1; DEFICIENCY; REGULATOR; INFLUX;
D O I
10.1007/s00018-018-2904-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4525 / 4537
页数:13
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