mitoBK.sub.Ca is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming

• Published in: eLife Vol. 12
• Main Authors: Bischof, Helmut, Maier, Selina, Koprowski, Piotr, Kulawiak, Bogusz, Burgstaller, Sandra, Jasinska, Joanna, Serafimov, Kristian, Zochowska, Monika, Gross, Dominic, Schroth, Werner, Matt, Lucas, Juarez Lopez, David Arturo, Zhang, Ying, Bonzheim, Irina, Büttner, Florian A, Fend, Falko, Schwab, Matthias, Birkenfeld, Andreas L, Malli, Roland, Lämmerhofer, Michael, Bednarczyk, Piotr, Szewczyk, Adam, Lukowski, Robert
• Format: Journal Article
• Language: English
• Published: eLife Science Publications, Ltd 29.05.2024
• Subjects: Breast cancer; Development and progression; Optical instruments industry; Scientific equipment and supplies industry; Canada; California; United States; Germany
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.92511

Alterations in the function of K.sup.+ channels such as the voltage- and Ca.sup.2+-activated K.sup.+ channel of large conductance (BK.sub.Ca) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK.sub.Ca splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK.sub.Ca). Through a combination of genetic knockdown and knockout along with a cell permeable BK.sub.Ca channel blocker, we show that mitoBK.sub.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.sub.Ca and BK.sub.Ca transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK.sub.Ca could represent a treatment strategy for selected BC patients in future.