转移相关蛋白（MTA）家族在乳腺癌的发生发展中发挥着至关重要的作用，乳腺癌是女性中发病率较高的常见恶性肿瘤。然而，人们对 MTA 家族每个成员促进乳腺癌进展的机制知之甚少。在本研究中，我们旨在研究MTA1、MTA3和含有三联基序的21（TRIM21）在体内乳腺癌细胞增殖、侵袭、上皮间质转化（EMT）和干细胞样特性中的作用和体外。使用染色质免疫沉淀 (ChIP)、荧光素酶报告基因、免疫沉淀 (IP) 和泛素化检测探讨了雌激素调节的 MTA1 和 MTA3/TRIM21 之间反馈环路的分子机制。这些发现表明，MTA1 通过抑制肿瘤抑制基因（包括 TRIM21 和 MTA3）的转录，充当促进乳腺癌进展的驱动因素。相反，MTA3 抑制 MTA1 转录，TRIM21 调节乳腺癌中 MTA1 蛋白的稳定性。雌激素破坏了 MTA1 和 MTA3 之间以及 MTA1 和 TRIM21 之间的平衡，从而影响乳腺癌的干性和 EMT 过程。这些发现表明，MTA1 通过与 MTA3 或 TRIM21 响应雌激素的负反馈环，在干细胞命运和 EMT 的分层调节网络中发挥着至关重要的作用，支持 MTA1、MTA3 和 TRIM21 作为潜在的预后生物标志物，并支持 MTA1 作为治疗靶点用于未来的乳腺癌治疗。© 2024。作者。

The metastasis-associated protein (MTA) family plays a crucial role in the development of breast cancer, a common malignancy with a high incidence rate among women. However, the mechanism by which each member of the MTA family contributes to breast cancer progression is poorly understood. In this study, we aimed to investigate the roles of MTA1, MTA3, and tripartite motif-containing 21 (TRIM21) in the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stem cell-like properties of breast cancer cells in vivo and in vitro. The molecular mechanisms of the feedback loop between MTA1 and MTA3/TRIM21 regulated by estrogen were explored using Chromatin immunoprecipitation (ChIP), luciferase reporter, immunoprecipitation (IP), and ubiquitination assays. These findings demonstrated that MTA1 acts as a driver to promote the progression of breast cancer by repressing the transcription of tumor suppressor genes, including TRIM21 and MTA3. Conversely, MTA3 inhibited MTA1 transcription and TRIM21 regulated MTA1 protein stability in breast cancer. Estrogen disrupted the balance between MTA1 and MTA3, as well as between MTA1 and TRIM21, thereby affecting stemness and the EMT processes in breast cancer. These findings suggest that MTA1 plays a vital role in stem cell fate and the hierarchical regulatory network of EMT through negative feedback loops with MTA3 or TRIM21 in response to estrogen, supporting MTA1, MTA3, and TRIM21 as potential prognostic biomarkers and MTA1 as a treatment target for future breast cancer therapies.© 2024. The Author(s).