Data from: Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds

The transcription factor FOXM1 is upregulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 signaling is also a key driver in many other cancers. Here, we identify a new class of compounds effective in suppressing FOXM1 activity in breast cancers, and displaying good potency for antitumor efficacy. The compounds bind directly to FOXM1 and alter its proteolytic sensitivity, reduce the cellular level of FOXM1 protein by a proteasome- dependent process, and suppress breast cancer cell proliferation and cell cycle progression and increase apoptosis. RNA-seq and gene set enrichment analyses indicate that the compounds decrease expression of FOXM1-regulated genes and suppress gene ontologies under FOXM1 regulation. Several compounds have favorable pharmacokinetic properties and show good tumor suppression in preclinical breast tumor models. These compounds may be suitable for further clinical evaluation in targeting aggressive breast cancers driven by FOXM1.
Supporting data are publicly available in the figshare repository: https://doi.org/10.6084/m9.figshare.10052219. RNA-Seq data of the effects of compounds and of siFOXM1 on global FOXM1 gene regulation, are publicly available in the NCBI Gene Expression Omnibus (GEO) repository: https://identifiers.org/geo:GSE132343. Uncropped Western blots are available as supplementary information. Resources in this dataset:Resource Title: Data availability. File Name: Web Page, url: https://doi.org/10.1038/s41523-019-0141-7 Datasets supporting Figs 1–6, Supplementary Table 1 and Supplementary Figs 1, 2, 4 and 5 in this published article are publicly available in the figshare repository: https://doi.org/10.6084/m9.figshare.10052219.17 RNA-Seq data of the effects of compounds and of siFOXM1 on global FOXM1 gene regulation, are publicly available in the NCBI Gene Expression Omnibus (GEO) repository: https://identifiers.org/geo:GSE132343.21 Uncropped Western blots are available as part of the supplementary information (Supplementary Fig. 8).

转录因子FOXM1在激素受体阳性及三阴性乳腺癌的侵袭性、耐药性亚型中表达上调，且与患者预后不良相关。FOXM1信号通路亦为多种癌症的关键驱动因素。本研究中，我们鉴定出一种新型化合物，能有效抑制乳腺癌中FOXM1的活性，并展现出良好的抗肿瘤效果。这些化合物直接结合于FOXM1，改变其蛋白水解敏感性，通过蛋白酶体依赖性途径降低细胞内FOXM1蛋白水平，并抑制乳腺癌细胞的增殖、细胞周期进程，并促进细胞凋亡。RNA测序和基因集富集分析表明，这些化合物降低了FOXM1调控基因的表达，并抑制了FOXM1调控下的基因本体。数种化合物具有优良的药代动力学特性，并在临床前乳腺癌肿瘤模型中显示出良好的肿瘤抑制作用。这些化合物可能适用于针对由FOXM1驱动的侵袭性乳腺癌的临床评估。支持数据可在figshare存储库中公开获取：https://doi.org/10.6084/m9.figshare.10052219。FOXM1基因全局调控的化合物和siFOXM1影响的RNA-Seq数据可在NCBI基因表达综合数据库（GEO）中公开获取：https://identifiers.org/geo:GSE132343。未裁剪的Western印迹作为补充信息提供。本数据集包含资源：资源标题：数据可用性。文件名：网页，URL：https://doi.org/10.1038/s41523-019-0141-7。支持本文图1-6、补充表1和补充图1、2、4和5的数據集可在figshare存储库中公开获取：https://doi.org/10.6084/m9.figshare.10052219.17。FOXM1基因全局调控的化合物和siFOXM1影响的RNA-Seq数据可在NCBI基因表达综合数据库（GEO）中公开获取：https://identifiers.org/geo:GSE132343.21。未裁剪的Western印迹作为补充信息的一部分提供。