Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer
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.
Authors
- Marc Thiry (ORCID: https://orcid.org/0000-0002-4944-584X)
- Ewelina Dondajewska (ORCID: https://orcid.org/0000-0001-9078-2015)
- Chloé Maurizy (ORCID: https://orcid.org/0000-0002-5176-7514)
- Quentin Lion (ORCID: https://orcid.org/0000-0002-9662-9318)
- Sandra Orménèse
- Kateryna Shostak (ORCID: https://orcid.org/0000-0002-9946-3536)
- Nathaniel F. Henneman
- Pierre Close (ORCID: https://orcid.org/0000-0002-8844-9616)
- Ivan Nemazanyy (ORCID: https://orcid.org/0000-0001-8080-839X)
- Alex von Kriegsheim (ORCID: https://orcid.org/0000-0002-4952-8573)
- Arnaud Lavergne (ORCID: https://orcid.org/0000-0003-4817-3202)
- Roopesh Krishnankutty (ORCID: https://orcid.org/0000-0002-1496-6135)
- Alexandre Hego (ORCID: https://orcid.org/0009-0007-7968-6795)
- Ganna Panasyuk (ORCID: https://orcid.org/0000-0002-5591-848X)
- Latifa Karim
- Alain Chariot (ORCID: https://orcid.org/0000-0002-1691-4347)
- Paula Allepuz‐Fuster
- Jair Marques (ORCID: https://orcid.org/0000-0002-8095-8475)
- Arnaud Blomme (ORCID: https://orcid.org/0000-0003-4183-8726)
Institutions
- Poznan University of Medical Sciences (PL)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Liège (BE)
- Université Paris Cité (FR)
- Edinburgh Cancer Research (GB)
- Institut Necker Enfants Malades (FR)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Structure fédérative de recherche Necker (FR)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1002/advs.202503022
- Citations
- 2
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Fonds De La Recherche Scientifique - FNRS
- Fonds Léon Fredericq
- Fondation contre le Cancer
- Walloon excellence in life sciences and biotechnology