mitoBK Ca is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming.
Helmut BischofSelina MaierPiotr KoprowskiBogusz KulawiakSandra BurgstallerJoanna JasińskaKristian SerafimovMonika ZochowskaDominic GrossWerner SchrothLucas MattDavid Arturo Juarez LopezYing ZhangIrina BonzheimFlorian A BüttnerFalko FendMatthias SchwabAndreas L BirkenfeldRoland MalliMichael LämmerhoferPiotr BednarczykAdam SzewczykRobert LukowskiPublished in: eLife (2024)
Alterations in the function of K + channels such as the voltage- and Ca 2+ -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.
Keyphrases
- protein kinase
- cell proliferation
- endothelial cells
- breast cancer cells
- end stage renal disease
- chronic kidney disease
- gene expression
- induced apoptosis
- single cell
- mesenchymal stem cells
- prognostic factors
- newly diagnosed
- cell death
- cell therapy
- endoplasmic reticulum stress
- induced pluripotent stem cells
- drug delivery
- replacement therapy
- wild type