School of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
Curr Probl Cancer. 2024 Aug;51:101118. doi: 10.1016/j.currproblcancer.2024.101118. Epub 2024 Jul 4.
To date, mounting evidence have shown that patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. The product of the MEN1 gene, menin, was also indicated to be an important regulator in breast cancer signaling network. Menin directly interacts with MLL, EZH2, JunD, NF-κB, PPARγ, VDR, Smad3, β-catenin and ERα to modulate gene transcriptions leading to cell proliferation inhibition. Moreover, interaction of menin-FANCD2 contributes to the enhancement of BRCA1-mediated DNA repair mechanism. Ectopic expression of menin causes Bax-, Bak- and Caspase-8-dependent apoptosis. However, despite numbers of menin inhibitors were exploited in other cancers, data on the usage of menin inhibitors in breast cancer treatment remain limited. In this review, we focused on the menin associated signaling pathways and gene transcription regulations, with the aim of elucidating its molecular mechanisms and of guiding the development of novel menin targeted drugs in breast cancer therapy.
迄今为止，越来越多的证据表明多发性内分泌肿瘤 1 型（MEN1）患者可能面临乳腺癌发生风险增加。MEN1 基因的产物 menin 也被表明是乳腺癌信号网络中的一个重要调节因子。Menin 直接与 MLL、EZH2、JunD、NF-κB、PPARγ、VDR、Smad3、β-catenin 和 ERα 相互作用，调节基因转录，从而抑制细胞增殖。此外，menin-FANCD2 的相互作用有助于增强 BRCA1 介导的 DNA 修复机制。menin 的异位表达导致 Bax、Bak 和 Caspase-8 依赖性细胞凋亡。然而，尽管在其他癌症中已经利用了许多 menin 抑制剂，但关于 menin 抑制剂在乳腺癌治疗中的应用的数据仍然有限。在这篇综述中，我们重点关注了与 menin 相关的信号通路和基因转录调控，旨在阐明其分子机制，并为乳腺癌治疗中新型靶向 menin 的药物的开发提供指导。
