Sodium regulates PLC and IP 3 R-mediated calcium signaling in invasive breast cancer cells.

Autor: James AD; Department of Biology, University of York, York, UK.; York Biomedical Research Institute, University of York, York, UK., Unthank KP; Department of Biology, University of York, York, UK., Jones I; Department of Biology, University of York, York, UK., Sajjaboontawee N; Department of Biology, University of York, York, UK.; York Biomedical Research Institute, University of York, York, UK., Sizer RE; Department of Biology, University of York, York, UK., Chawla S; Department of Biology, University of York, York, UK.; York Biomedical Research Institute, University of York, York, UK., Evans GJO; Department of Biology, University of York, York, UK.; York Biomedical Research Institute, University of York, York, UK., Brackenbury WJ; Department of Biology, University of York, York, UK.; York Biomedical Research Institute, University of York, York, UK.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2023 Apr; Vol. 11 (7), pp. e15663.
DOI: 10.14814/phy2.15663
Abstrakt: Intracellular Ca 2+ signaling and Na + homeostasis are inextricably linked via ion channels and co-transporters, with alterations in the concentration of one ion having profound effects on the other. Evidence indicates that intracellular Na + concentration ([Na + ] i ) is elevated in breast tumors, and that aberrant Ca 2+ signaling regulates numerous key cancer hallmark processes. The present study therefore aimed to determine the effects of Na + depletion on intracellular Ca 2+ handling in metastatic breast cancer cell lines. The relationship between Na + and Ca 2+ was probed using fura-2 and SBFI fluorescence imaging and replacement of extracellular Na + with equimolar N-methyl-D-glucamine (0Na + /NMDG) or choline chloride (0Na + /ChoCl). In triple-negative MDA-MB-231 and MDA-MB-468 cells and Her2+ SKBR3 cells, but not ER+ MCF-7 cells, 0Na + /NMDG and 0Na + /ChoCl resulted in a slow, sustained depletion in [Na + ] i that was accompanied by a rapid and sustained increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ). Application of La 3+ in nominal Ca 2+ -free conditions had no effect on this response, ruling out reverse-mode NCX activity and Ca 2+ entry channels. Moreover, the Na + -linked [Ca 2+ ] i increase was independent of membrane potential hyperpolarization (NS-1619), but was inhibited by pharmacological blockade of IP 3 receptors (2-APB), phospholipase C (PLC, U73122) or following depletion of endoplasmic reticulum Ca 2+ stores (cyclopiazonic acid). Thus, Na + is linked to PLC/IP 3 -mediated activation of endoplasmic reticulum Ca 2+ release in metastatic breast cancer cells and this may have an important role in breast tumors where [Na + ] i is perturbed.
(© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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