Academic Journal
Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer
| العنوان: | Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer |
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| المؤلفون: | Prekovic, Stefan, Schuurman, Karianne, Mayayo-Peralta, Isabel, Manjón, Anna G., Buijs, Mark, Yavuz, Selçuk, Wellenstein, Max D., Barrera, Alejandro, Monkhorst, Kim, Huber, Anne, Morris, Ben, Lieftink, Cor, Chalkiadakis, Theofilos, Alkan, Ferhat, Silva, Joana, Győrffy, Balázs, Hoekman, Liesbeth, van den Broek, Bram, Teunissen, Hans, Debets, Donna O., Severson, Tesa, Jonkers, Jos, Reddy, Timothy, de Visser, Karin E., Faller, William, Beijersbergen, Roderick, Altelaar, Maarten, de Wit, Elzo, Medema, Rene, Zwart, Wilbert |
| المصدر: | Prekovic , S , Schuurman , K , Mayayo-Peralta , I , Manjón , A G , Buijs , M , Yavuz , S , Wellenstein , M D , Barrera , A , Monkhorst , K , Huber , A , Morris , B , Lieftink , C , Chalkiadakis , T , Alkan , F , Silva , J , Győrffy , B , Hoekman , L , van den Broek , B , Teunissen , H , Debets , D O , Severson , T , Jonkers , J , Reddy , T , de Visser .... |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Animals, Antineoplastic Agents/pharmacology, Cell Cycle/genetics, Cell Line, Tumor, Cell Proliferation/drug effects, Cell Survival/drug effects, Chromatin/genetics, Chromatin Immunoprecipitation Sequencing, Chromosomal Proteins, Non-Histone/genetics, Cyclin-Dependent Kinase Inhibitor p57/genetics, Enhancer Elements, Genetic, Gene Expression Regulation, Neoplastic/drug effects, Glucocorticoids/pharmacology, Humans, Imidazoles/pharmacology, Immunohistochemistry, Lung Neoplasms/genetics, Mice, Proteomics, Pyrazines/pharmacology, RNA, Small Interfering, RNA-Seq, Receptor, IGF Type 1/metabolism, Receptors |
| الوصف: | The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR activation might also have anti-proliferative action on tumours, the underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the mechanisms of glucocorticoid response, focusing on lung cancer. We show that GR activation induces reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. GR-induced dormancy is dependent on a single GR-target gene, CDKN1C, regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anticancer therapy related side-effects. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.1038/s41467-021-24537-3 |
| الاتاحة: | https://research.tue.nl/en/publications/77cf3ddc-3d1d-4ff3-af8e-9dbb7b232893 https://doi.org/10.1038/s41467-021-24537-3 https://pure.tue.nl/ws/files/176616584/s41467_021_24537_3.pdf http://www.scopus.com/inward/record.url?scp=85110858166&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ADBB4375 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-021-24537-3 |
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