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SHR Neuro Cancer Cardio Lipid Metab Microb

Gross, D; Bischof, H; Maier, S; Sporbeck, K; Birkenfeld, AL; Malli, R; Ruth, P; Proikas-Cezanne, T; Lukowski, R.
IK_Ca channels control breast cancer metabolism including AMPK-driven autophagy.
Cell Death Dis. 2022; 13(10): 902 Doi: 10.1038/s41419-022-05329-z [OPEN ACCESS]
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Co-authors Med Uni Graz: Bischof Helmut; Malli Roland
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Abstract:: Ca²⁺-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 Ca²⁺- 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 Ca²⁺- 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.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; Mice - administration & dosage; Adenosine Triphosphate - metabolism; AMP-Activated Protein Kinases - metabolism; Autophagy - administration & dosage; Glycolysis - administration & dosage; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism; Breast Neoplasms - metabolism