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IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy
Ca(2+)-activated K(+) channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613901/ https://www.ncbi.nlm.nih.gov/pubmed/36302750 http://dx.doi.org/10.1038/s41419-022-05329-z |
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author | Gross, Dominic Bischof, Helmut Maier, Selina Sporbeck, Katharina Birkenfeld, Andreas L. Malli, Roland Ruth, Peter Proikas-Cezanne, Tassula Lukowski, Robert |
author_facet | Gross, Dominic Bischof, Helmut Maier, Selina Sporbeck, Katharina Birkenfeld, Andreas L. Malli, Roland Ruth, Peter Proikas-Cezanne, Tassula Lukowski, Robert |
author_sort | Gross, Dominic |
collection | PubMed |
description | Ca(2+)-activated K(+) channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K(+)- and Ca(2+)- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca(2+)- and K(+)-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy. |
format | Online Article Text |
id | pubmed-9613901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96139012022-10-29 IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy Gross, Dominic Bischof, Helmut Maier, Selina Sporbeck, Katharina Birkenfeld, Andreas L. Malli, Roland Ruth, Peter Proikas-Cezanne, Tassula Lukowski, Robert Cell Death Dis Article Ca(2+)-activated K(+) channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K(+)- and Ca(2+)- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca(2+)- and K(+)-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy. Nature Publishing Group UK 2022-10-27 /pmc/articles/PMC9613901/ /pubmed/36302750 http://dx.doi.org/10.1038/s41419-022-05329-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gross, Dominic Bischof, Helmut Maier, Selina Sporbeck, Katharina Birkenfeld, Andreas L. Malli, Roland Ruth, Peter Proikas-Cezanne, Tassula Lukowski, Robert IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title | IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title_full | IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title_fullStr | IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title_full_unstemmed | IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title_short | IK(Ca) channels control breast cancer metabolism including AMPK-driven autophagy |
title_sort | ik(ca) channels control breast cancer metabolism including ampk-driven autophagy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613901/ https://www.ncbi.nlm.nih.gov/pubmed/36302750 http://dx.doi.org/10.1038/s41419-022-05329-z |
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