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FOXM1 通过依赖 YAP1 的方式促进乳腺癌细胞干性和迁移。

FOXM1 facilitates breast cancer cell stemness and migration in YAP1-dependent manner.

机构信息

College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing, 100124, China.

College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100(#), District of Chaoyang, Beijing, 100124, China.

出版信息

Arch Biochem Biophys. 2020 May 30;685:108349. doi: 10.1016/j.abb.2020.108349. Epub 2020 Mar 21.

Abstract

Breast cancer has the highest incidence and mortality in the female population. Forkhead box M1 (FOXM1) known as a transcription factor is upregulated and associated with poor prognosis in a variety of cancers. However, the molecular mechanisms of FOXM1 on breast cancer progression are poorly understood. In this study, we found that FOXM1 was up-regulated in breast cancer. FOXM1 promoted cell proliferation, clonal formation, and migration capacity in triple negative breast cancer by increasing transcriptional activity of YAP1. FOXM1 also maintained cell stemness via the Hippo pathway. The YAP1-TEAD binding inhibitor Verteporfin reduced the transcription level of OCT4 and NANOG but the Hippo pathway activator XMU-MP-1 could increase the transcription level of OCT4 and NANOG. In summary, our findings indicated that FOXM1 promoted breast cancer progression through the Hippo pathway, and it was suggested a new strategy to treat breast cancer.

摘要

乳腺癌在女性人群中的发病率和死亡率最高。叉头框 M1(FOXM1)作为一种转录因子,在多种癌症中上调并与不良预后相关。然而,FOXM1 对乳腺癌进展的分子机制仍不清楚。在这项研究中,我们发现 FOXM1 在乳腺癌中上调。FOXM1 通过增加 YAP1 的转录活性,促进三阴性乳腺癌细胞的增殖、克隆形成和迁移能力。FOXM1 还通过 Hippo 通路维持细胞干性。YAP1-TEAD 结合抑制剂 Verteporfin 降低了 OCT4 和 NANOG 的转录水平,而 Hippo 通路激活剂 XMU-MP-1 可以增加 OCT4 和 NANOG 的转录水平。总之,我们的研究结果表明,FOXM1 通过 Hippo 通路促进乳腺癌的进展,这为治疗乳腺癌提供了一种新的策略。

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