Nature Communications (Jul 2021)
Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer
- Stefan Prekovic,
- Karianne Schuurman,
- Isabel Mayayo-Peralta,
- Anna G. Manjón,
- Mark Buijs,
- Selçuk Yavuz,
- Max D. Wellenstein,
- Alejandro Barrera,
- Kim Monkhorst,
- Anne Huber,
- Ben Morris,
- Cor Lieftink,
- Theofilos Chalkiadakis,
- Ferhat Alkan,
- Joana Silva,
- Balázs Győrffy,
- Liesbeth Hoekman,
- Bram van den Broek,
- Hans Teunissen,
- Donna O. Debets,
- Tesa Severson,
- Jos Jonkers,
- Timothy Reddy,
- Karin E. de Visser,
- William Faller,
- Roderick Beijersbergen,
- Maarten Altelaar,
- Elzo de Wit,
- Rene Medema,
- Wilbert Zwart
Affiliations
- Stefan Prekovic
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Karianne Schuurman
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Isabel Mayayo-Peralta
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Anna G. Manjón
- Division of Cell Biology, Oncode Institute, The Netherlands Cancer Institute
- Mark Buijs
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Selçuk Yavuz
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Max D. Wellenstein
- Division of Tumour Biology and Immunology, Oncode Institute, The Netherlands Cancer Institute
- Alejandro Barrera
- Department of Biostatistics & Bioinformatics, and Centre for Genomic & Computational Biology, Duke University Medical Centre
- Kim Monkhorst
- Department of Pathology, The Netherlands Cancer Institute
- Anne Huber
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Ben Morris
- Division of Molecular Carcinogenesis and Robotics and Screening Centre, Netherlands Cancer Institute
- Cor Lieftink
- Division of Molecular Carcinogenesis and Robotics and Screening Centre, Netherlands Cancer Institute
- Theofilos Chalkiadakis
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Ferhat Alkan
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Joana Silva
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Balázs Győrffy
- Semmelweis University Department of Bioinformatics and 2nd Department of Pediatrics
- Liesbeth Hoekman
- Mass spectrometry/Proteomics Facility, The Netherlands Cancer Institute
- Bram van den Broek
- Division of Cell Biology and BioImaging Facility, The Netherlands Cancer Institute
- Hans Teunissen
- Division of Gene Regulation, Oncode Institute, The Netherlands Cancer Institute
- Donna O. Debets
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
- Tesa Severson
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Jos Jonkers
- Division of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute
- Timothy Reddy
- Department of Biostatistics & Bioinformatics, and Centre for Genomic & Computational Biology, Duke University Medical Centre
- Karin E. de Visser
- Division of Tumour Biology and Immunology, Oncode Institute, The Netherlands Cancer Institute
- William Faller
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Roderick Beijersbergen
- Division of Molecular Carcinogenesis and Robotics and Screening Centre, Netherlands Cancer Institute
- Maarten Altelaar
- Mass spectrometry/Proteomics Facility, The Netherlands Cancer Institute
- Elzo de Wit
- Division of Gene Regulation, Oncode Institute, The Netherlands Cancer Institute
- Rene Medema
- Division of Cell Biology, Oncode Institute, The Netherlands Cancer Institute
- Wilbert Zwart
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- DOI
- https://doi.org/10.1038/s41467-021-24537-3
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 18
Abstract
Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.
