An image-based screen for secreted proteins involved in breast cancer G0 cell cycle arrest.

Autor: Weston WA; MRC Laboratory of Medical Sciences, Imperial College London, Du Cane Road, London, W12 0HS, UK., Holt JA; MRC Laboratory of Medical Sciences, Imperial College London, Du Cane Road, London, W12 0HS, UK.; Institute of Clinical Sciences, Imperial College London, Du Cane Road, London, W12 0HS, UK., Wiecek AJ; UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK., Pilling J; Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB2 0AA, UK., Schiavone LH; Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Gothenburg, Sweden., Smith DM; Emerging Innovation Unit, Discovery Sciences, R&D, AstraZeneca, Cambridge, CB2 0AA, UK., Secrier M; UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK., Barr AR; MRC Laboratory of Medical Sciences, Imperial College London, Du Cane Road, London, W12 0HS, UK. a.barr@ic.ac.uk.; Institute of Clinical Sciences, Imperial College London, Du Cane Road, London, W12 0HS, UK. a.barr@ic.ac.uk.
Jazyk: angličtina
Zdroj: Scientific data [Sci Data] 2024 Aug 10; Vol. 11 (1), pp. 868. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1038/s41597-024-03697-z
Abstrakt: Secreted proteins regulate the balance between cellular proliferation and G0 arrest and therefore play important roles in tumour dormancy. Tumour dormancy presents a significant clinical challenge for breast cancer patients, where non-proliferating, G0-arrested cancer cells remain at metastatic sites, below the level of clinical detection, some of which can re-enter proliferation and drive tumour relapse. Knowing which secreted proteins can regulate entry into and exit from G0 allows us to manipulate their signalling to prevent tumour relapse. To identify novel secreted proteins that can promote breast cancer G0 arrest, we performed a secretome-wide, image-based screen for proteins that increase the fraction of cells in G0 arrest. From a secretome library of 1282 purified proteins, we identified 29 candidates that promote G0 arrest in non-transformed and transformed breast epithelial cells. The assay we have developed can be adapted for use in other perturbation screens in other cell types. All datasets have been made available for re-analysis and our candidate proteins are presented for alternative bioinformatic refinement or further experimental follow up.
(© 2024. The Author(s).)
Databáze: MEDLINE
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