Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1071037/full |
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| author | Riccardo Filadi Riccardo Filadi Agnese De Mario Matteo Audano Patrizia Romani Silvia Pedretti Cesar Cardenas Cesar Cardenas Cesar Cardenas Cesar Cardenas Sirio Dupont Cristina Mammucari Cristina Mammucari Nico Mitro Nico Mitro Paola Pizzo Paola Pizzo |
| author_facet | Riccardo Filadi Riccardo Filadi Agnese De Mario Matteo Audano Patrizia Romani Silvia Pedretti Cesar Cardenas Cesar Cardenas Cesar Cardenas Cesar Cardenas Sirio Dupont Cristina Mammucari Cristina Mammucari Nico Mitro Nico Mitro Paola Pizzo Paola Pizzo |
| author_sort | Riccardo Filadi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:06:57Z |
| format | Article |
| id | doaj.art-280b7091289047958911523f7c7ceea5 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T04:06:57Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-280b7091289047958911523f7c7ceea52023-03-13T05:13:17ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-03-011110.3389/fcell.2023.10710371071037Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolismRiccardo Filadi0Riccardo Filadi1Agnese De Mario2Matteo Audano3Patrizia Romani4Silvia Pedretti5Cesar Cardenas6Cesar Cardenas7Cesar Cardenas8Cesar Cardenas9Sirio Dupont10Cristina Mammucari11Cristina Mammucari12Nico Mitro13Nico Mitro14Paola Pizzo15Paola Pizzo16Neuroscience Institute, National Research Council (CNR), Padua, ItalyDepartment of Biomedical Sciences, University of Padova, Padua, ItalyDepartment of Biomedical Sciences, University of Padova, Padua, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyDepartment of Molecular Medicine (DMM), University of Padova, Padua, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyFaculty of Sciences, Universidad Mayor, Center for Integrative Biology, Santiago, ChileGeroscience Center for Brain Health and Metabolism, Santiago, ChileBuck Institute for Research on Aging, Novato, CA, United StatesDepartment of Chemistry and Biochemistry, University of California, Santa Barbara, CA, United StatesDepartment of Molecular Medicine (DMM), University of Padova, Padua, ItalyDepartment of Biomedical Sciences, University of Padova, Padua, ItalyMyology Center (CIR-Myo), University of Padova, Padua, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy0Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyNeuroscience Institute, National Research Council (CNR), Padua, ItalyDepartment of Biomedical Sciences, University of Padova, Padua, ItalyRewiring 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1071037/fullIP3Ca2+breast cancerTNBCmitochondriaMCU |
| spellingShingle | Riccardo Filadi Riccardo Filadi Agnese De Mario Matteo Audano Patrizia Romani Silvia Pedretti Cesar Cardenas Cesar Cardenas Cesar Cardenas Cesar Cardenas Sirio Dupont Cristina Mammucari Cristina Mammucari Nico Mitro Nico Mitro Paola Pizzo Paola Pizzo Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism Frontiers in Cell and Developmental Biology IP3 Ca2+ breast cancer TNBC mitochondria MCU |
| title | Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| title_full | Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| title_fullStr | Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| title_full_unstemmed | Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| title_short | Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| title_sort | sustained ip3 linked ca2 signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism |
| topic | IP3 Ca2+ breast cancer TNBC mitochondria MCU |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1071037/full |
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