Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Agnese De Mario¹  Cristina Mammucari²  Patrizia Romani³  Sirio Dupont³  Silvia Pedretti⁴  Matteo Audano⁴  Nico Mitro⁵  Cesar Cardenas⁶  Riccardo Filadi⁷  Paola Pizzo⁷ 

[1] Department of Biomedical Sciences, University of Padova, Padua, Italy;Department of Biomedical Sciences, University of Padova, Padua, Italy;Myology Center (CIR-Myo), University of Padova, Padua, Italy;Department of Molecular Medicine (DMM), University of Padova, Padua, Italy;Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy;Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy;Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy;Faculty of Sciences, Universidad Mayor, Center for Integrative Biology, Santiago, Chile;Geroscience Center for Brain Health and Metabolism, Santiago, Chile;Buck Institute for Research on Aging, Novato, CA, United States;Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, United States;Neuroscience Institute, National Research Council (CNR), Padua, Italy;Department of Biomedical Sciences, University of Padova, Padua, Italy;

关键词: IP3;    Ca;    breast cancer;    TNBC;    mitochondria;    MCU;    fatty acids;    acylcarnitine;   

DOI  :  10.3389/fcell.2023.1071037

 received in 2022-10-15, accepted in 2023-03-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

Rewiring of mitochondrial metabolism has been described in different cancers as a key step for their progression. Calcium (Ca2+) signaling regulates mitochondrial function and is known to be altered in several malignancies, including triple negative breast cancer (TNBC). However, whether and how the alterations in Ca2+ signaling contribute to metabolic changes in TNBC has not been elucidated. Here, we found that TNBC cells display frequent, spontaneous inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations, which are sensed by mitochondria. By combining genetic, pharmacologic and metabolomics approaches, we associated this pathway with the regulation of fatty acid (FA) metabolism. Moreover, we demonstrated that these signaling routes promote TNBC cell migration in vitro, suggesting they might be explored to identify potential therapeutic targets.

【 授权许可】

Unknown   
Copyright © 2023 Filadi, De Mario, Audano, Romani, Pedretti, Cardenas, Dupont, Mammucari, Mitro and Pizzo.