MAF 扩增会增加乳腺癌 (BCa) 转移的风险，其机制目前仍知之甚少，但具有重要的临床意义。雌激素受体阳性 (ER) BCa 的生长和转移都需要雌激素，尽管其机制不为人所知。在这里，我们整合了人类和同基因小鼠 BCa 模型的蛋白质组学、转录组学、表观基因组学、染色质可及性和功能测定，以表明 MAF 直接与雌激素受体 α (ERα) 相互作用，从而促进有利于转移扩散的独特染色质景观。我们确定了在雌激素暴露后以 MAF 依赖性方式重新获得许可的促进转移基因。组蛋白去甲基化酶 KDM1A 是表观基因组重塑的关键，可促进促转移 MAF/雌激素驱动的基因表达程序的表达，KDM1A 活性的丧失可防止这种转移。因此，我们确定，MAF/雌激素介导的转移的分子基础需要来自全身环境的遗传、表观遗传和激素信号，这些信号影响 BCa 细胞的转移能力。© 2023。作者。

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.© 2023. The Author(s).