Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer
Abstract Cancer cells adapt their metabolism to support aberrant cell proliferation. However, the functional link between metabolic reprogramming and cell cycle progression remains largely unexplored. Mitochondria rely on the transfer of multiple lipids from the endoplasmic reticulum (ER) to their m...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202503022 |
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| author | Ewelina Dondajewska Paula Allepuz‐Fuster Chloé Maurizy Alexandre Hego Sandra Ormenese Quentin Lion Arnaud Blomme Pierre Close Arnaud Lavergne Latifa Karim Marc Thiry Ivan Nemazanyy Roopesh Krishnankutty Jair Marques Jr Alex vonKriegsheim Nathaniel F. Henneman Ganna Panasyuk Kateryna Shostak Alain Chariot |
| author_facet | Ewelina Dondajewska Paula Allepuz‐Fuster Chloé Maurizy Alexandre Hego Sandra Ormenese Quentin Lion Arnaud Blomme Pierre Close Arnaud Lavergne Latifa Karim Marc Thiry Ivan Nemazanyy Roopesh Krishnankutty Jair Marques Jr Alex vonKriegsheim Nathaniel F. Henneman Ganna Panasyuk Kateryna Shostak Alain Chariot |
| author_sort | Ewelina Dondajewska |
| collection | DOAJ |
| description | Abstract Cancer cells adapt their metabolism to support aberrant cell proliferation. However, the functional link between metabolic reprogramming and cell cycle progression remains largely unexplored. Mitochondria rely on the transfer of multiple lipids from the endoplasmic reticulum (ER) to their membranes to be functional. Several mitochondrial‐derived metabolites influence cancer cell proliferation by modulating the epigenome. Here, the loss of STARD7, a lipid transfer protein whose expression is enhanced in breast cancer, is shown to lead a metabolic reprogramming characterized by the accumulation of carnitine derivatives and S‐Adenosyl‐L‐methionine (SAM). Elevated SAM levels cause the increase of H3K27 trimethylation on many gene promoters coding for candidates involved in cell cycle progression. Likewise, STARD7 deficiency triggers cell cycle arrest and impairs ERα‐dependent cell proliferation. Moreover, EGFR signaling is also impaired in triple negative breast cancer cells lacking STARD7, at least due to deregulated EGFR trafficking to lysosomes. Therefore, mitochondria rely on STARD7 to support cell cycle progression in breast cancer. |
| format | Article |
| id | doaj-art-76fe231cf8b74ce6aaa963d9535873bf |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-76fe231cf8b74ce6aaa963d9535873bf2025-08-23T14:12:31ZengWileyAdvanced Science2198-38442025-08-011231n/an/a10.1002/advs.202503022Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast CancerEwelina Dondajewska0Paula Allepuz‐Fuster1Chloé Maurizy2Alexandre Hego3Sandra Ormenese4Quentin Lion5Arnaud Blomme6Pierre Close7Arnaud Lavergne8Latifa Karim9Marc Thiry10Ivan Nemazanyy11Roopesh Krishnankutty12Jair Marques Jr13Alex vonKriegsheim14Nathaniel F. Henneman15Ganna Panasyuk16Kateryna Shostak17Alain Chariot18Laboratory of Cancer Biology Liège BelgiumLaboratory of Cancer Biology Liège BelgiumLaboratory of Cancer Biology Liège BelgiumGIGA Flow Cytometry and Cell Imaging Platform University of Liege Liege BelgiumGIGA Flow Cytometry and Cell Imaging Platform University of Liege Liege BelgiumLaboratory of Cancer Biology Liège BelgiumGIGA Cancer GIGA University of Liege CHU Sart‐Tilman Liège 4000 BelgiumGIGA Cancer GIGA University of Liege CHU Sart‐Tilman Liège 4000 BelgiumGIGA Genomics Platform University of Liege Liege BelgiumGIGA Genomics Platform University of Liege Liege BelgiumUnit of Cell and Tissue Biology GIGA Neurosciences University of Liege Liege BelgiumPlatform for Metabolic Analyses Structure Fédérative de Recherche Necker INSERM US24/CNRS UAR 3633 Paris 75015 FranceInstitute of Genetics and Cancer Edinburgh Cancer Research ScotlandInstitute of Genetics and Cancer Edinburgh Cancer Research ScotlandInstitute of Genetics and Cancer Edinburgh Cancer Research ScotlandInstitut Necker‐Enfants Malades (INEM) INSERM U1151/CNRS UMR 8253, 75015 Paris France and Université de Paris Cité Paris 75006 FranceInstitut Necker‐Enfants Malades (INEM) INSERM U1151/CNRS UMR 8253, 75015 Paris France and Université de Paris Cité Paris 75006 FranceLaboratory of Cancer Biology Liège BelgiumLaboratory of Cancer Biology Liège BelgiumAbstract Cancer cells adapt their metabolism to support aberrant cell proliferation. However, the functional link between metabolic reprogramming and cell cycle progression remains largely unexplored. Mitochondria rely on the transfer of multiple lipids from the endoplasmic reticulum (ER) to their membranes to be functional. Several mitochondrial‐derived metabolites influence cancer cell proliferation by modulating the epigenome. Here, the loss of STARD7, a lipid transfer protein whose expression is enhanced in breast cancer, is shown to lead a metabolic reprogramming characterized by the accumulation of carnitine derivatives and S‐Adenosyl‐L‐methionine (SAM). Elevated SAM levels cause the increase of H3K27 trimethylation on many gene promoters coding for candidates involved in cell cycle progression. Likewise, STARD7 deficiency triggers cell cycle arrest and impairs ERα‐dependent cell proliferation. Moreover, EGFR signaling is also impaired in triple negative breast cancer cells lacking STARD7, at least due to deregulated EGFR trafficking to lysosomes. Therefore, mitochondria rely on STARD7 to support cell cycle progression in breast cancer.https://doi.org/10.1002/advs.202503022breast cancercell cycle arrestEGFR signalinglipid transfer proteinmetabolic reprogramming |
| spellingShingle | Ewelina Dondajewska Paula Allepuz‐Fuster Chloé Maurizy Alexandre Hego Sandra Ormenese Quentin Lion Arnaud Blomme Pierre Close Arnaud Lavergne Latifa Karim Marc Thiry Ivan Nemazanyy Roopesh Krishnankutty Jair Marques Jr Alex vonKriegsheim Nathaniel F. Henneman Ganna Panasyuk Kateryna Shostak Alain Chariot Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer Advanced Science breast cancer cell cycle arrest EGFR signaling lipid transfer protein metabolic reprogramming |
| title | Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer |
| title_full | Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer |
| title_fullStr | Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer |
| title_full_unstemmed | Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer |
| title_short | Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer |
| title_sort | loss of stard7 triggers metabolic reprogramming and cell cycle arrest in breast cancer |
| topic | breast cancer cell cycle arrest EGFR signaling lipid transfer protein metabolic reprogramming |
| url | https://doi.org/10.1002/advs.202503022 |
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