Data from: Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds
dataset
posted on 2024-02-13, 13:56authored byYvonne Ziegler, Mary J. Laws, Valeria Sanabria Guillen, Sung Hoon Kim, Parama Dey, Brandi P. Smith, Ping Gong, Noah Bindman, Yuechao Zhao, Kathryn Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, Dorraya El-Ashry, Zeynep Madak-Erdogan, John A. Katzenellenbogen, Benita S. Katzenellenbogen
<p>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.</p>
<p>Supporting data are publicly available in the figshare repository: <a href="https://doi.org/10.6084/m9.figshare.10052219">https://doi.org/10.6084/m9.figshare.10052219</a>. 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: <a href="https://identifiers.org/geo:GSE132343">https://identifiers.org/geo:GSE132343</a>. Uncropped Western blots are available as supplementary information. </p><div><br>Resources in this dataset:</div><br><ul><li><p>Resource Title: Data availability.</p> <p>File Name: Web Page, url: <a href="https://doi.org/10.1038/s41523-019-0141-7">https://doi.org/10.1038/s41523-019-0141-7</a> </p><p>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: <a href="https://doi.org/10.6084/m9.figshare.10052219.17">https://doi.org/10.6084/m9.figshare.10052219.17</a> 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: <a href="https://identifiers.org/geo:GSE132343.21">https://identifiers.org/geo:GSE132343.21</a> Uncropped Western blots are available as part of the supplementary information (Supplementary Fig. 8).</p></li></ul><p></p>
breast neoplasms; neoplasms; transcription factors; patients; proteolysis; cell proliferation; cell cycle; apoptosis; sequence analysis; genes; pharmacokinetics; models; clinical examination; gene expression; Western blotting; Health and Pathology; Biological Sciences
Pending citation
No
Public Access Level
Public
Preferred dataset citation
Ziegler, Yvonne; Laws, Mary J.; Guillen, Valeria Sanabria; Kim, Sung Hoon; Dey, Parama; Smith, Brandi P.; Gong, Ping; Bindman, Noah; Zhao, Yuechao; Carlson, Kathryn; Yasuda, Mayuri A.; Singh, Divya; Li, Zhong; El-Ashry, Dorraya; Madak-Erdogan, Zeynep; Katzenellenbogen, John A.; Katzenellenbogen, Benita S. (2020). Data from: Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds. npj Breast Cancer.