NCS-1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin
Journal Title
Molecular Oncology
Publication Type
Journal Article in press
Abstract
Neuronal calcium sensor-1 (NCS-1) is a positive modulator of IP3 receptors and was recently associated with poorer survival in breast cancers. However, the association between NCS-1 and breast cancer molecular subtypes and the effects of NCS-1 silencing on calcium signaling in breast cancer cells remains unexplored. Herein we report for the first time an increased expression of NCS-1 in breast cancers of the basal molecular subtype, a subtype associated with poor prognosis. Using MDA-MB-231 basal breast cancer cells expressing the GCaMP6m Ca(2+) indicator, we showed that NCS-1 silencing did not result in major changes in cytosolic free Ca(2+) increases as a result of ER Ca(2+) store mobilization. However, NCS-1 silencing suppressed unstimulated basal Ca(2+) influx. NCS-1 silencing in MDA-MB-231 cells also promoted necrotic cell death induced by the chemotherapeutic drug doxorubicin (1 microM). The effect of NCS-1 silencing on cell death was phenocopied by silencing of ORAI1, a Ca(2+) store-operated Ca(2+) channel that maintains Ca(2+) levels in the endoplasmic reticulum Ca(2+) store and whose expression was significantly positively correlated with NCS-1 in clinical breast cancer samples. This newly identified association between NCS-1 and basal breast cancers, together with the identification of the role of NCS-1 in the regulation of the effects of doxorubicin in MDA-MB-231 breast cancer cells, suggest that NCS-1 and/or pathways regulated by NCS-1 may be important in the treatment of basal breast cancers in women.
Publisher
Wiley
WEHI Research Division(s)
Cancer Biology And Stem Cells
PubMed ID
31647602
Open Access at Publisher's Site
https://doi.org/10.1002/1878-0261.12589
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-10-28 12:05:01
Last Modified: 2019-10-30 09:26:27
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