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2023-11-09

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/219118

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

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https://doi.org/10.1038/s41556-023-01281-y

Resum

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.

Matèries

Càncer de mama, Estrògens, Factors de transcripció

Matèries (anglès)

Breast cancer, Estrogen, Transcription factors

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Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

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.. MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis. . _Nature Cell Biology_. 2023. [consulta: 26 de febrer de 2026]. ISSN: 1465-7392. [Disponible a: https://hdl.handle.net/2445/219118]

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