The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics
Abstract The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lin...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88666-1 |
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| author | Szonja Polett Pósa Éva Saskői Lili Bársony Lőrinc Pongor Fanni Fekete János Papp Anikó Bozsik Attila Patócs Henriett Butz |
| author_facet | Szonja Polett Pósa Éva Saskői Lili Bársony Lőrinc Pongor Fanni Fekete János Papp Anikó Bozsik Attila Patócs Henriett Butz |
| author_sort | Szonja Polett Pósa |
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| description | Abstract The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple in vitro functional assays and transcriptome sequencing. GR activation increased cell motility in TN but not in ER + tumour cells, as observed in both collective and single-cell migration tests. Time-lapse analysis showed enhanced motility after 4–6 h in wound healing, despite dex inhibiting migration initially. This inhibition was observed at 2 h in single-cell tracking migration assays. Cell proliferation increased in TN and decreased in ER + cells upon GR activation, reversed by GR antagonist. RNA sequencing revealed dex’s impact on cell adhesion and extracellular matrix signalling in TN cells and on DNA replication in ER + cells. Based on data from 1085 human breast cancer specimens, GR pathway expression correlated with migratory, extracellular matrix, and angiogenesis gene signatures. Additionally, higher expression of GR and increased GR signature were observed in fast-migrating cells compared to slow-migrating ones. Positive correlation between the GR signature and migration signature at the single-cell level indicated an association between GR activity and cell migration. For the first time, we assessed altered time-lapse migration dynamics in TN breast cancer cells, potentially contributing to cancer progression and prognosis, highlighting that the effects of dexamethasone on breast cancer cell migration are influenced by ER status and treatment duration. |
| format | Article |
| id | doaj-art-f94099b452524af5a6a5e723be5cb1d7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-f94099b452524af5a6a5e723be5cb1d72025-02-09T12:35:25ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-88666-1The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamicsSzonja Polett Pósa0Éva Saskői1Lili Bársony2Lőrinc Pongor3Fanni Fekete4János Papp5Anikó Bozsik6Attila Patócs7Henriett Butz8Department of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyCancer Genomics and Epigenetics Core Group, HCEMMDepartment of Oncology Biobank, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyDepartment of Molecular Genetics and the National Tumor Biology Laboratory, National Institute of OncologyAbstract The glucocorticoid receptor (GR) plays a significant role in breast cancer cell behaviour, although data on its effects are conflicting. The impact of GR agonist dexamethasone (dex) and antagonist mifepristone (mif) on oestrogen-positive (ER+) and triple-negative (TN) breast cancer cell lines in both 2D and 3D cultures was studied using multiple in vitro functional assays and transcriptome sequencing. GR activation increased cell motility in TN but not in ER + tumour cells, as observed in both collective and single-cell migration tests. Time-lapse analysis showed enhanced motility after 4–6 h in wound healing, despite dex inhibiting migration initially. This inhibition was observed at 2 h in single-cell tracking migration assays. Cell proliferation increased in TN and decreased in ER + cells upon GR activation, reversed by GR antagonist. RNA sequencing revealed dex’s impact on cell adhesion and extracellular matrix signalling in TN cells and on DNA replication in ER + cells. Based on data from 1085 human breast cancer specimens, GR pathway expression correlated with migratory, extracellular matrix, and angiogenesis gene signatures. Additionally, higher expression of GR and increased GR signature were observed in fast-migrating cells compared to slow-migrating ones. Positive correlation between the GR signature and migration signature at the single-cell level indicated an association between GR activity and cell migration. For the first time, we assessed altered time-lapse migration dynamics in TN breast cancer cells, potentially contributing to cancer progression and prognosis, highlighting that the effects of dexamethasone on breast cancer cell migration are influenced by ER status and treatment duration.https://doi.org/10.1038/s41598-025-88666-1GlucocorticoidGlucocorticoid receptorBreast cancerMigrationTranscriptomeGene expression |
| spellingShingle | Szonja Polett Pósa Éva Saskői Lili Bársony Lőrinc Pongor Fanni Fekete János Papp Anikó Bozsik Attila Patócs Henriett Butz The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics Scientific Reports Glucocorticoid Glucocorticoid receptor Breast cancer Migration Transcriptome Gene expression |
| title | The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics |
| title_full | The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics |
| title_fullStr | The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics |
| title_full_unstemmed | The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics |
| title_short | The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics |
| title_sort | impact of glucocorticoid receptor transactivation on context dependent cell migration dynamics |
| topic | Glucocorticoid Glucocorticoid receptor Breast cancer Migration Transcriptome Gene expression |
| url | https://doi.org/10.1038/s41598-025-88666-1 |
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