MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis

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  • dc.contributor.author Llorente, Alicia
  • dc.contributor.author Ballaré, Cecilia Julia
  • dc.contributor.author Blanco, Enrique
  • dc.contributor.author Di Croce, Luciano
  • dc.contributor.author Gomis, Roger R.
  • dc.date.accessioned 2024-02-09T07:49:59Z
  • dc.date.available 2024-02-09T07:49:59Z
  • dc.date.issued 2023
  • dc.description.abstract MAF amplification increases the risk of breast cancer (BCa) metastasis through mechanisms that are still poorly understood yet have important clinical implications. Oestrogen-receptor-positive (ER+) BCa requires oestrogen for both growth and metastasis, albeit by ill-known mechanisms. Here we integrate proteomics, transcriptomics, epigenomics, chromatin accessibility and functional assays from human and syngeneic mouse BCa models to show that MAF directly interacts with oestrogen receptor alpha (ERα), thereby promoting a unique chromatin landscape that favours metastatic spread. We identify metastasis-promoting genes that are de novo licensed following oestrogen exposure in a MAF-dependent manner. The histone demethylase KDM1A is key to the epigenomic remodelling that facilitates the expression of the pro-metastatic MAF/oestrogen-driven gene expression program, and loss of KDM1A activity prevents this metastasis. We have thus determined that the molecular basis underlying MAF/oestrogen-mediated metastasis requires genetic, epigenetic and hormone signals from the systemic environment, which influence the ability of BCa cells to metastasize.
  • dc.description.sponsorship We also thank V. Raker for her editing support. A.L. and I.E. are supported by FPI-SO grants and A.B. and C.F.-P. by FPI Fellowship grants from Gobierno de España. M.F. is supported by the Horizon 2020 Research and Innovation Programme under Marie Skłodowska–Curie grant agreement no. 955951; M.T.B. is supported by an AECC (Spanish Cancer Association) postdoctoral grant, M.N. and R.R.G. by an AECC grant Proyecto GCTRA18006CARR. R.R.G. and L.D.C. are supported by the Institució Catalana de Recerca i Estudis Avançats. Special thanks go to Carme Segura Capellades for generously supporting our endeavours. Support and structural funds were provided by the Generalitat de Catalunya (2021-SGR-00909) to R.R.G., and by the BBVA Foundation, Fundación Científica AECC (PRYGN223207GOMI), the ISCIII/FEDER-CIBERONC, the ‘la Caixa’ Foundation (ID 100010434) under agreement HR17-00092, the FERO Foundation, the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (CIBERONC and PID2019-104948RB-I00; PID2022-143093OB-100) to R.R.G. Work in the L.D.C. laboratory is supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) (PID2019-108322GB-100) and from AGAUR. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Llorente A, Blasco MT, Espuny I, Guiu M, Ballaré C, Blanco E et al. MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis. Nat Cell Biol. 2023 Dec;25(12):1833-47. DOI: 10.1038/s41556-023-01281-y
  • dc.identifier.doi http://dx.doi.org/10.1038/s41556-023-01281-y
  • dc.identifier.issn 1465-7392
  • dc.identifier.uri http://hdl.handle.net/10230/59046
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Cell Biol. 2023 Dec;25(12):1833-47
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/955951
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104948RB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-143093OB-100
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-108322GB-100
  • dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Breast cancer
  • dc.subject.keyword Cancer epigenetics
  • dc.subject.keyword Metastasis
  • dc.title MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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