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Calcium signalling in hypoxia-induced epithelial-mesenchymal transition in breast cancer cells [Poster]
Citation
Azimi, I and Davis, FM and Paraic, AK and Thompson, EW and Roberts-Thomson, SJ and Monteith, GR, Calcium signalling in hypoxia-induced epithelial-mesenchymal transition in breast cancer cells [Poster], Proceedings of the 13th International Meeting of the European Calcium Society, 13-17 September 2014, Aix-en-Provence, France, pp. 55. (2014) [Conference Extract]
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Abstract
Hypoxia as a hallmark of the cancer microenvironment
induces epithelial-mesenchymal transition (EMT) in breast
cancer cells, a process whereby cancer cells acquire a
more invasive phenotype. We have recently characterised
the remodelling of calcium (Ca2+) signalling as a
consequence of EMT induced by epidermal growth factor
(EGF). In this study we aimed to characterise the
remodelling of Ca2+ signalling in a model of hypoxia-induced EMT in MDA-MB-468 breast cancer cells. The
induction of EMT by hypoxia (1% O2) was confirmed by
assessing the protein level of vimentin (after 48 h hypoxia)
and mRNA levels of some of other EMT markers including
vimentin, Snail, Twist, N-cadherin and the CD44/CD24
ratio (after 24 h hypoxia). The mRNA levels of fifty Ca2+
pumps, Ca 2+ channels and receptors in the presence and
absence of hypoxia (24 h) were assessed using real time
RT-PCR. This led to identification of four specific targets
which were significantly up-regulated in hypoxia compared
to normoxia (21% O2), including P2Y6. This purinergic
receptor, showed a three-fold mRNA induction by hypoxia.
Pharmacological inhibition of P2Y6 by its selective inhibitor
MRS2578, significantly reduced cellular migration of the
mesenchymal like MDA-MB-231 breast cancer cell line.
Gene expression profiling of 458 breast tumours revealed
elevation of P2Y6 in basal breast cancer subtypes
compared to other subtypes. Furthermore, breast cancer
patients with high P2Y6 levels showed reduced overall
survival rates compared to patients with low levels of P2Y6
(total patient number = 1115, P-value = 0.019). In
conclusion, alterations in Ca2+ signalling and P2Y6
purinergic receptor expression is a feature of hypoxia-induced EMT. Further studies are required to identify if a
specific Ca2+pump, Ca2+ channel or receptor may
represent a target for the mesenchymal phenotype of
breast cancer cells and offer a therapeutic strategy for the
control of breast cancer metastasis.
Item Details
Item Type: | Conference Extract |
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Keywords: | Calcium signalling, hypoxia, EMT, breast cancer |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Pharmacology and pharmaceutical sciences |
Research Field: | Basic pharmacology |
Objective Division: | Expanding Knowledge |
Objective Group: | Expanding knowledge |
Objective Field: | Expanding knowledge in the health sciences |
UTAS Author: | Azimi, I (Dr Iman Azimi) |
ID Code: | 151221 |
Year Published: | 2014 |
Deposited By: | Pharmacy |
Deposited On: | 2022-07-25 |
Last Modified: | 2022-07-28 |
Downloads: | 0 |
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