Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer

Katzenellenbogen, Benita S.; Guillen, Valeria Sanabria; Katzenellenbogen, John A.

doi:10.1186/s13058-023-01675-8

Cited by 16 publications

(11 citation statements)

References 98 publications

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“…Furthermore, this study also revealed that the expression levels of key regulatory genes downstream of the ER, namely, MYC and FOXM1 , are influenced by BPA, consequently affecting the expression of cell cycle-related genes. Both MYC and FOXM1 are widely recognized oncogenes closely associated with tumor growth and metastasis, and the EGFR, AP-1 and P53 pathways, which were shown to be disrupted by BPA in this study, also play crucial roles in cancer initiation and progression. , Thus, from a health implication, this study’s results corroborate the correlation between BPA exposure and cancer development. Additionally, the upregulation of regulatory genes related to lipid metabolism, such as PPARG , SREBP1 , and CEBPA , as well as the nonmonotonic impact of BPA on cell cycle-related genes may provide insight into why BPA leads to an increase in body weight at low doses and a decrease at high doses in rodents .…”

Section: Results and Discussionsupporting

confidence: 81%

“…Comparing the findings of this study with those of previous publications, it is evident that BPA can work as an endocrinedisrupting chemical and affect ER-related pathways. 116 Furthermore, this study also revealed that the expression levels 117 and the EGFR, AP-1 and P53 pathways, which were shown to be disrupted by BPA in this study, also play crucial roles in cancer initiation and progression. 91,118 Thus, from a health implication, this study's results corroborate the correlation between BPA exposure and cancer development.…”

Section: Biological Significance Of the Processes And Pathwayssupporting

confidence: 61%

“…116 Furthermore, this study also revealed that the expression levels of key regulatory genes downstream of the ER, namely, MYC and FOXM1, are influenced by BPA, consequently affecting the expression of cell cycle-related genes. Both MYC and FOXM1 are widely recognized oncogenes closely associated with tumor growth and metastasis, 117 and the EGFR, AP-1 and P53 pathways, which were shown to be disrupted by BPA in this study, also play crucial roles in cancer initiation and progression. 91,118 Thus, from a health implication, this study's results corroborate the correlation between BPA exposure and cancer development.…”

Section: Biological Significance Of the Processes And Pathwaysmentioning

confidence: 61%

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Transcriptomic Integration Analyses Uncover Common Bisphenol A Effects Across Species and Tissues Primarily Mediated by Disruption of JUN/FOS, EGFR, ER, PPARG, and P53 Pathways

Yang,

Lu,

Yin

et al. 2023

Environ. Sci. Technol.

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Bisphenol A (BPA) is a common endocrine disruptor widely used in the production of electronic, sports, and medical equipment, as well as consumer products like milk bottles, dental sealants, and thermal paper. Despite its widespread use, current assessments of BPA exposure risks remain limited due to the lack of comprehensive cross-species comparative analyses. To address this gap, we conducted a study aimed at identifying genes and fundamental molecular processes consistently affected by BPA in various species and tissues, employing an effective data integration method and bioinformatic analyses. Our findings revealed that exposure to BPA led to significant changes in processes like lipid metabolism, proliferation, and apoptosis in the tissues/cells of mammals, fish, and nematodes. These processes were found to be commonly affected in adipose, liver, mammary, uterus, testes, and ovary tissues. Additionally, through an in-depth analysis of signaling pathways influenced by BPA in different species and tissues, we observed that the JUN/FOS, EGFR, ER, PPARG, and P53 pathways, along with their downstream key transcription factors and kinases, were all impacted by BPA. Our study provides compelling evidence that BPA indeed induces similar toxic effects across different species and tissues. Furthermore, our investigation sheds light on the underlying molecular mechanisms responsible for these toxic effects. By uncovering these mechanisms, we gain valuable insights into the potential health implications associated with BPA exposure, highlighting the importance of comprehensive assessments and awareness of this widespread endocrine disruptor.

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Section: Results and Discussionsupporting

confidence: 81%

Section: Biological Significance Of the Processes And Pathwayssupporting

confidence: 61%

Section: Biological Significance Of the Processes And Pathwaysmentioning

confidence: 61%

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Transcriptomic Integration Analyses Uncover Common Bisphenol A Effects Across Species and Tissues Primarily Mediated by Disruption of JUN/FOS, EGFR, ER, PPARG, and P53 Pathways

Yang,

Lu,

Yin

et al. 2023

Environ. Sci. Technol.

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“…Among the top CRISPR-essential MRs, Forkhead box M1 (FOXM1) emerged as the most conserved across DMG samples, suggesting it may play a critical role in regulating DMG cell state and nominating it as a candidate therapeutic target 42 ( Fig. 2f ).…”

Section: Resultsmentioning

confidence: 99%

Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations

Fernández,

Tomassoni,

Zhang

et al. 2024

Preprint

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Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

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“…Twelve genes (AKT1, CCND1, ERBB2, ESR1, MTOR, IRS1, JAK2, NOS3, PTEN, RAF1, STAT1, and STAT3) were involved in leptin signaling pathway, which is related to breast cancer malignancy [83, 84]. Five genes (BIRC5, CCND1, ESR1, RB1, and CHEK2) were involved in PID FOXM1 PATHWAY, which has been reported as a crucial oncogenic transcription factor that promotes breast cancer progression and growth [85, 86].…”

Section: Resultsmentioning

confidence: 99%

maGENEgerZ: An Efficient AI-Based Framework Can Extract More Expressed Genes and Biological Insights Underlying Breast Cancer Drug Response Mechanism

Turki,

Taguchi

2023

Preprint

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Understanding breast cancer drug response mechanism can play a crucial role in improving the treatment outcomes and survival rates. Existing bioinformatics-based approaches are far from perfect and do not adopt computational methods based on advanced artificial intelligence concepts. Therefore, we introduce a novel computational framework based on an efficient version of support vector machines (esvm) working as follows. First, we downloaded and processed three gene expression datasets related to breast cancer responding and non-responding to the treatments from the gene expression omnibus (GEO) according to the following GEO accession numbers: GSE130787, GSE140494, and GSE196093. Our method esvm is formulated as a constrained optimization problem in the dual form as a function of λ. We recover the importance of each gene as a function of λ, y, and x. Then, we select p genes out of n, provided as input to enrichment analysis tools, Enrichr and Metascape. Compared to existing baseline methods, results demonstrate superiority and efficiency of esvm achieving high performance results and having more expressed genes in (1) well-established breast cancer cell lines including MD-MB231, MCF7, and HS578T; and (2) breast tissues. Moreover, esvm is able to identify (1) various drugs including clinically approved ones (e.g., tamoxifen and erlotinib); (2) seventy-four unique genes (including tumor suppression genes such as TP53 and BRCA1); and (3) thirty-six unique TFs (including SP1 and RELA). These results have been reported to be linked to breast cancer drug response mechanism, progression, and metastasizing. Our method is available publicly in the maGENEgerZ web server at https://aibio.shinyapps.io/maGENEgerZ/.

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Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer

Cited by 16 publications

References 98 publications

Transcriptomic Integration Analyses Uncover Common Bisphenol A Effects Across Species and Tissues Primarily Mediated by Disruption of JUN/FOS, EGFR, ER, PPARG, and P53 Pathways

Transcriptomic Integration Analyses Uncover Common Bisphenol A Effects Across Species and Tissues Primarily Mediated by Disruption of JUN/FOS, EGFR, ER, PPARG, and P53 Pathways

Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations

maGENEgerZ: An Efficient AI-Based Framework Can Extract More Expressed Genes and Biological Insights Underlying Breast Cancer Drug Response Mechanism

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