线粒体代谢重构已被描述为不同癌症进展的关键步骤。钙（Ca2+）信号调节线粒体功能，已知在多种恶性肿瘤中发生改变，包括三阴性乳腺癌（TNBC）。然而，Ca2+信号改变是否以及如何促进TNBC代谢变化尚未阐明。在这里，我们发现TNBC细胞频繁、自发的肌醇1,4,5-三磷酸（IP3）依赖性Ca2+振荡，这些振荡被线粒体感应。通过将基因、药物和代谢组学方法相结合，我们将这条途径与脂肪酸（FA）代谢的调节联系起来。此外，我们证明了这些信号途径促进了TNBC细胞在体外的迁移，暗示它们可能被探究以寻找潜在的治疗靶标。版权所有©2023 Filadi、De Mario、Audano、Romani、Pedretti、Cardenas、Dupont、Mammucari、Mitro和Pizzo。

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