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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...

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Detalles Bibliográficos
Autores principales: Gross, Dominic, Bischof, Helmut, Maier, Selina, Sporbeck, Katharina, Birkenfeld, Andreas L., Malli, Roland, Ruth, Peter, Proikas-Cezanne, Tassula, Lukowski, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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
Descripción
Sumario: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.