MAF amplification licenses ER α through epigenetic remodelling to drive breast cancer metastasis
Nat Cell Biol. 2023 Nov 9. doi: 10.1038/s41556-023-01281-y. Online ahead of print.ABSTRACTMAF 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.PMID:37945904 | DOI:10.1038/s41556-023-01281-y
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Alicia Llorente Mar ía Teresa Blasco Irene Espuny Marc Guiu Cecilia Ballar é Enrique Blanco Adri à Caballé Anna Bellmunt Fernando Salvador Andrea Morales Marc Nu ñez Guillem Loren Francesca Imbastari Marta Fidalgo Cristina Figueras-Puig Patrizia Gibl Source Type: research