西班牙巴塞罗那科学技术研究所Roger R. Gomis研究组提出，MAF扩增通过表观遗传重塑许可ERα驱动乳腺癌(BCa)转移。该研究于2023年11月9日发表于国际一流学术期刊《自然—细胞生物学》杂志上。

他们整合了蛋白质组学、转录组学、表观基因组学、染色质可及性和人类和同基因小鼠BCa模型的功能分析，表明MAF直接与雌激素受体α (ERα)相互作用，从而促进了一种独特的染色质景观，有利于转移扩散。他们确定了在雌激素暴露后以MAF依赖方式重新许可的促进转移的基因。

组蛋白去甲基化酶KDM1A是表观基因组重塑的关键，它促进了促转移性MAF/雌激素驱动基因表达程序的表达，而KDM1A活性的丧失阻止了这种转移。因此，他们已经确定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细胞转移的能力。

研究人员表示，MAF扩增增加BCa转移的风险，其机制尚不清楚，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，尽管其机制尚不清楚。

附：英文原文

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

Author: Llorente, Alicia, Blasco, Mara Teresa, Espuny, Irene, Guiu, Marc, Ballar, Cecilia, Blanco, Enrique, Caball, Adri, Bellmunt, Anna, Salvador, Fernando, Morales, Andrea, Nuez, Marc, Loren, Guillem, Imbastari, Francesca, Fidalgo, Marta, Figueras-Puig, Cristina, Gibler, Patrizia, Graupera, Mariona, Monteiro, Freddy, Riera, Antoni, Holen, Ingunn, Avgustinova, Alexandra, Di Croce, Luciano, Gomis, Roger R.

Issue&Volume: 2023-11-09

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. Llorente, Blasco, Espuny and colleagues show that MAF regulates the genomic distribution of ERα and modulates the expression of metastasis genes via KDM1A, thereby driving metastatic spread in breast cancer.

DOI: 10.1038/s41556-023-01281-y

Source: https://www.nature.com/articles/s41556-023-01281-y