ArticleThe Journal of biological chemistry2012
Distinct regulation of cytoplasmic calcium signals and cell death pathways by different plasma membrane calcium ATPase isoforms in MDA-MB-231 breast cancer cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 72 citations in OpenAlex.
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- Lapatinib-Resistant HER2+ Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone.International journal of molecular sciences · 2025Article
- Dysregulation of calcium homeostasis in cancer and its role in chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2024Review
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- PMCA inhibition reverses drug resistance in clinically refractory cancer patient-derived models.BMC medicine · 2023Article
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- Active nNOS Is Required for Grp94-Induced Antioxidant Cytoprotection: A Lesson from Myogenic to Cancer Cells.International journal of molecular sciences · 2022Article
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- Calcium Signalling in Breast Cancer Associated Bone Pain.International journal of molecular sciences · 2022Review
- The Effect of Cyclosporine A on Proteins Controlling Intracellular Calcium Concentration in Breast Cancer Cells.The Journal of membrane biology · 2022Article
- Cytotoxic effect of carbohydrate derivatives of digitoxigenin involves modulation of plasma membrane CaJournal of cellular biochemistry · 2021Article
- Genome-wide DNA methylome and whole-transcriptome landscapes of spontaneous intraductal papilloma in tree shrews.Annals of translational medicine · 2021Article
- Article
- The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells.Exploration of targeted anti-tumor therapy · 2021Article
- Targeting the Calcium Signalling Machinery in Cancer.Cancers · 2020Review
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- Plasma Membrane CaCancers · 2020Article
- NCS-1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin.Molecular oncology · 2020Article
- CaAdvances in cancer research · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma membrane calcium ATPases (PMCAs) actively extrude Ca(2+) from the cell and are essential components in maintaining intracellular Ca(2+) homeostasis. There are four PMCA isoforms (PMCA1-4), and alternative splicing of the PMCA genes creates a suite of calcium efflux pumps. The role of these different PMCA isoforms in the control of calcium-regulated cell death pathways and the significance of the expression of multiple isoforms of PMCA in the same cell type are not well understood. In these studies, we assessed the impact of PMCA1 and PMCA4 silencing on cytoplasmic free Ca(2+) signals and cell viability in MDA-MB-231 breast cancer cells. The PMCA1 isoform was the predominant regulator of global Ca(2+) signals in MDA-MB-231 cells. PMCA4 played only a minor role in the regulation of bulk cytosolic Ca(2+), which was more evident at higher Ca(2+) loads. Although PMCA1 or PMCA4 knockdown alone had no effect on MDA-MB-231 cell viability, silencing of these isoforms had distinct consequences on caspase-independent (ionomycin) and -dependent (ABT-263) cell death. PMCA1 knockdown augmented necrosis mediated by the Ca(2+) ionophore ionomycin, whereas apoptosis mediated by the Bcl-2 inhibitor ABT-263 was enhanced by PMCA4 silencing. PMCA4 silencing was also associated with an inhibition of NFκB nuclear translocation, and an NFκB inhibitor phenocopied the effects of PMCA4 silencing in promoting ABT-263-induced cell death. This study demonstrates distinct roles for PMCA1 and PMCA4 in the regulation of calcium signaling and cell death pathways despite the widespread distribution of these two isoforms. The targeting of some PMCA isoforms may enhance the effectiveness of therapies that act through the promotion of cell death pathways in cancer cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.