EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer
Abstract Cellular plasticity enables cancer cells to adapt non-genetically, thereby preventing therapeutic success. The epithelial-mesenchymal transition (EMT) is a type of plasticity linked to resistance and metastasis. However, its exact impact on population diversity and its dynamics under chemot...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Cancer Cell International |
| Online Access: | https://doi.org/10.1186/s12935-025-03637-w |
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| author | Lauriane Muller Frédérique Fauvet Christelle Chassot Francesca Angileri Angèle Coutant Cyril Dégletagne Laurie Tonon Pierre Saintigny Alain Puisieux Anne-Pierre Morel Maria Ouzounova Pierre Martinez |
| author_facet | Lauriane Muller Frédérique Fauvet Christelle Chassot Francesca Angileri Angèle Coutant Cyril Dégletagne Laurie Tonon Pierre Saintigny Alain Puisieux Anne-Pierre Morel Maria Ouzounova Pierre Martinez |
| author_sort | Lauriane Muller |
| collection | DOAJ |
| description | Abstract Cellular plasticity enables cancer cells to adapt non-genetically, thereby preventing therapeutic success. The epithelial-mesenchymal transition (EMT) is a type of plasticity linked to resistance and metastasis. However, its exact impact on population diversity and its dynamics under chemotherapy is unknown. We used single-cell transcriptomics to investigate phenotypic diversity dynamics upon treatment in two in vitro models of triple negative breast cancer (TNBC), where EMT-driven plasticity is either induced or spontaneously occurring. We report that EMT-driven plasticity confers higher phenotypic cell–cell variability (p < 0.001) while enriching for stem-like cells. Genetic and phenotypic cell–cell variability were not consistently correlated. High-plasticity populations displayed more pre-adapted cells before treatment (p = 0.03). In a population displaying spontaneous EMT and phenotypic variation, pre-adapted cells were a rare minority of high-scoring outliers whose expression patterns correlated with survival in TNBC patients subjected to chemotherapy (p = 0.03). Higher plasticity was not associated with a partial EMT status. Our results provide novel insights on how EMT-driven plasticity promotes a prospective diversification process increasing population phenotypic diversity, which can yield rare pre-adapted states before treatment. This highlights the need to tackle phenotypic diversity prior to treatment in high-plasticity tumours. |
| format | Article |
| id | doaj-art-eca5a85b1c0c4dd1a4f311beedc5a749 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-eca5a85b1c0c4dd1a4f311beedc5a7492025-02-09T12:55:23ZengBMCCancer Cell International1475-28672025-02-0125111510.1186/s12935-025-03637-wEMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancerLauriane Muller0Frédérique Fauvet1Christelle Chassot2Francesca Angileri3Angèle Coutant4Cyril Dégletagne5Laurie Tonon6Pierre Saintigny7Alain Puisieux8Anne-Pierre Morel9Maria Ouzounova10Pierre Martinez11Integrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1EMT and Cancer Cell Plasticity Team, Centre Léon BérardEMT and Cancer Cell Plasticity Team, Centre Léon BérardIntegrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Integrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Plateforme de Génomique des Cancers, Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052, CNRS UMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Plateforme de Bioinformatique Gilles Thomas, Synergie Lyon Cancer, Centre Léon BérardIntegrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Equipe Labellisée Ligue Contre le Cancer, CNRS UMR 3666, INSERM U1143EMT and Cancer Cell Plasticity Team, Centre Léon BérardEMT and Cancer Cell Plasticity Team, Centre Léon BérardIntegrated Analyses of Cancer Dynamics Team, Centre de Recherche en Cancérologie de Lyon (CRCL), Institut Convergence PlasCan, INSERM U1052, CNRSUMR 5286, Centre Léon Bérard, Université Claude Bernard Lyon 1Abstract Cellular plasticity enables cancer cells to adapt non-genetically, thereby preventing therapeutic success. The epithelial-mesenchymal transition (EMT) is a type of plasticity linked to resistance and metastasis. However, its exact impact on population diversity and its dynamics under chemotherapy is unknown. We used single-cell transcriptomics to investigate phenotypic diversity dynamics upon treatment in two in vitro models of triple negative breast cancer (TNBC), where EMT-driven plasticity is either induced or spontaneously occurring. We report that EMT-driven plasticity confers higher phenotypic cell–cell variability (p < 0.001) while enriching for stem-like cells. Genetic and phenotypic cell–cell variability were not consistently correlated. High-plasticity populations displayed more pre-adapted cells before treatment (p = 0.03). In a population displaying spontaneous EMT and phenotypic variation, pre-adapted cells were a rare minority of high-scoring outliers whose expression patterns correlated with survival in TNBC patients subjected to chemotherapy (p = 0.03). Higher plasticity was not associated with a partial EMT status. Our results provide novel insights on how EMT-driven plasticity promotes a prospective diversification process increasing population phenotypic diversity, which can yield rare pre-adapted states before treatment. This highlights the need to tackle phenotypic diversity prior to treatment in high-plasticity tumours.https://doi.org/10.1186/s12935-025-03637-w |
| spellingShingle | Lauriane Muller Frédérique Fauvet Christelle Chassot Francesca Angileri Angèle Coutant Cyril Dégletagne Laurie Tonon Pierre Saintigny Alain Puisieux Anne-Pierre Morel Maria Ouzounova Pierre Martinez EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer Cancer Cell International |
| title | EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer |
| title_full | EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer |
| title_fullStr | EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer |
| title_full_unstemmed | EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer |
| title_short | EMT-driven plasticity prospectively increases cell–cell variability to promote therapeutic adaptation in breast cancer |
| title_sort | emt driven plasticity prospectively increases cell cell variability to promote therapeutic adaptation in breast cancer |
| url | https://doi.org/10.1186/s12935-025-03637-w |
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