Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Bischof, H; Maier, S; Koprowski, P; Kulawiak, B; Burgstaller, S; Jasińska, J; Serafimov, K; Zochowska, M; Gross, D; Schroth, W; Matt, L; Juarez, Lopez, DA; Zhang, Y; Bonzheim, I; Büttner, FA; Fend, F; Schwab, M; Birkenfeld, AL; Malli, R; Lämmerhofer, M; Bednarczyk, P; Szewczyk, A; Lukowski, R.
mitoBK_Ca is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming.
Elife. 2024; 12: RP92511 Doi: 10.7554/eLife.92511 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Führende Autor*innen der Med Uni Graz: Bischof Helmut
Co-Autor*innen der Med Uni Graz: Burgstaller Sandra; Malli Roland
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Abstract:: Alterations in the function of K⁺ channels such as the voltage- and Ca²⁺-activated K⁺ channel of large conductance (BK_Ca) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK_Ca splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK_Ca). Through a combination of genetic knockdown and knockout along with a cell permeable BK_Ca channel blocker, we show that mitoBK_Ca modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the 'Warburg effect', thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBK_Ca and BK_Ca transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK_Ca could represent a treatment strategy for selected BC patients in future.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Animals - administration & dosage; Mice - administration & dosage; Breast Neoplasms - genetics, pathology, metabolism; Cell Line, Tumor - administration & dosage; Cell Proliferation - administration & dosage; Mitochondria - metabolism, genetics; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism, genetics; Mitochondrial Membranes - metabolism; Female - administration & dosage; Energy Metabolism - administration & dosage
Find related publications in this database (Keywords): K+ channels; Kcnma1; mitoBK(Ca); Slo1; breast cancer; metabolic reprogramming; biosensors; Warburg effect; Human; Mouse