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

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 integr...

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Detalles Bibliográficos
Autores: Llorente Lope, Alicia, Blasco, M. T., Espuny, Irene, Guiu, Marc, Ballaré, C., Blanco, E., Caballé, A., Bellmunt, Anna, Salvador, F., Morales, A., Nuñez, M., Loren, Guillem, Imbastari, Francesca, Fidalgo, Marta, Figueras-Puig, Cristina, Gibler, Patrizia, Graupera, M., Monteiro, F., Riera i Escalé, Antoni, Holen, I., Avgustinova, A., Di Croce, L., Gomis, R. R.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/219115
Acceso en línea:https://hdl.handle.net/2445/219115
http://hdl.handle.net/2445/219115
Access Level:acceso abierto
Palabra clave:Càncer de mama
Estrògens
Factors de transcripció
Breast cancer
Estrogen
Transcription factors
Descripción
Sumario: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.

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