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Calcium signalling in hypoxia-induced epithelial-mesenchymal transition in breast cancer cells [Poster]
conference contribution
posted on 2023-05-24, 21:15 authored by Iman AzimiIman Azimi, Davis, FM, Paraic, AK, Thompson, EW, Roberts-Thomson, SJ, Monteith, GRHypoxia 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.
History
Publication title
Proceedings of the 13th International Meeting of the European Calcium SocietyPagination
55Department/School
School of Pharmacy and PharmacologyEvent title
13th International Meeting of the European Calcium Society (ECS2014)Event Venue
Aix-en-Provence, FranceDate of Event (Start Date)
2014-09-13Date of Event (End Date)
2014-09-17Repository Status
- Restricted