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http://bura.brunel.ac.uk/handle/2438/27688| Title: | The mitotic checkpoint kinase BUB1 is a direct and actionable target of MYB in adenoid cystic carcinoma |
| Other Titles: | Identification of the mitotic checkpoint kinase BUB1 is a direct and actionable target of MYB in adenoid cystic carcinoma |
| Authors: | Cicirò, Y Ragusa, D Nevado, PT Lattanzio, R Sala, G Des Rochers, T Millard, M Andersson, M Stenman, G Sala, A |
| Keywords: | adenoid cystic carcinoma;head and neck cancer;MYB;BUB1;3D assay;BAY1816032;PDX;RNA sequencing;ChIP sequencing |
| Issue Date: | 19-Dec-2023 |
| Publisher: | Wiley on behalf of Federation of European Biochemical Societies |
| Citation: | Cicirò, Y et al. (2024) 'The mitotic checkpoint kinase BUB1 is a direct and actionable target of MYB in adenoid cystic carcinoma', FEBS Letters, 598 (2), pp. 252 - 265. doi: 10.1111/andr.13582. |
| Abstract: | Copyright © 2023 The Authors. Adenoid cystic carcinoma (ACC) is a head and neck cancer that frequently originates in salivary glands, but can also strike other exocrine glands such as the breast. A key molecular alteration found in the majority of ACC cases is MYB gene rearrangements, leading to activation of the oncogenic transcription factor MYB. In this study, we used immortalised breast epithelial cells and an inducible MYB transgene as a model of ACC. Molecular profiling confirmed that MYB-driven gene expression causes a transition into an ACC-like state. Using this new cell model, we identified BUB1 as a targetable kinase directly controlled by MYB, whose pharmacological inhibition caused MYB-dependent synthetic lethality, growth arrest and apoptosis of patient-derived cells and organoids. |
| Description: | Data accessibility:
ChIP-seq data on ACCX11 cells are available at ArrayExpress accession E-MTAB-12976. Microarray datasets were downloaded from the Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/) repository. The Andersson dataset (GEO accession number GSE88804) reported expression data of 13 surgical samples of ACC and 7 NSG samples [[8]]. The Chowbina dataset (GEO accession number GSE36820) presented microarray analysis on 3 normal samples and 11 ACC xenograft samples. The Gao dataset (GEO accession number GSE59702) contains expression profiling by array of 12 ACC with matched normal tissues [[9]]. RNAseq data from Cicirò dataset report 7 replicates of ACC samples (ACCX11) and 3 NSG samples; data available at ArrayExpress accession E-MTAB-12978. RNAseq data of MM MYB/EV ± DOX are available at ArrayExpress accession E-MTAB-12977. Supporting Information is available onloine at: https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14786#support-information-section . |
| URI: | https://bura.brunel.ac.uk/handle/2438/27688 |
| DOI: | https://doi.org/10.1111/andr.13582 |
| Other Identifiers: | ORCID iD: Denise Ragusa https://orcid.org/0000-0002-0303-8683 ORCID iD: Gianluca Sala https://orcid.org/0000-0002-4494-915X ORCID iD: Mattias K. Andersson https://orcid.org/0000-0001-6391-2048 ORCID iD: Arturo Sala https://orcid.org/0000-0002-2841-7866 |
| Appears in Collections: | Dept of Life Sciences Research Papers |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| FullText.pdf | Copyright © 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | 3.12 MB | Adobe PDF | View/Open |
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