ArticleBreast cancer (Tokyo, Japan)2022
Serotonin 5-HT7 receptor is a biomarker poor prognostic factor and induces proliferation of triple-negative breast cancer cells through FOXM1.
Article in Breast cancer (Tokyo, Japan), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Repurposing neurological drugs for brain cancer therapeutics: A systematic approach to identify charged molecules for affinity-based local drug delivery systems.International journal of pharmaceutics · 2025Pooled it
- Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.International journal of molecular sciences · 2024Pooled it
- FOXM1 Drives Subtype-Specific Dysregulation of Prognostic miRNAs in Breast Cancer Cells.Journal of clinical practice and research · 2026Article
- Review
- Research on the effects of desflurane and sevoflurane on proliferation and migration of breast cancer cells.Scientific reports · 2026Article
- Design, Synthesis, Biological Evaluation, and Molecular Modeling Studies of Novel 2-Aminothiazole Derivatives as Potential FOXM1 Inhibitors for Triple-Negative Breast Cancer Therapy and Structure-Activity Relationship.Drug development research · 2026Article
- miR-484 sensitizes in IDH-wild and IDH-mutant glioblastoma cells to temozolomide by inhibiting oncogenic FOXM1 signaling.Cancer cell international · 2026Article
- The molecular footprint of the serotoninergic system in human glioblastoma cells.Journal of molecular histology · 2025Article
- Neurotransmitter Regulatory Networks: A New Perspective on Cancer Therapy.Biomolecules · 2025Review
- Metabolomics as a tool for understanding and treating triple-negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Review
- Antagonism of 5-HT7 Receptors as a Promising Target for Gastric Cancer via Apoptotic Pathway.Journal of biochemical and molecular toxicology · 2025Article
- miR-484 as an "OncomiR" in Breast Cancer Promotes Tumorigenesis by Suppressing Apoptosis Genes.Annals of surgical oncology · 2025Article
- Comprehensive bioinformatic analysis of HTR7: A potential biomarker for diagnosis, survival, and immunotherapy in pan-cancer.PloS one · 2025Article
- Novel benzothiazole/benzothiazole thiazolidine-2,4-dione derivatives as potential FOXM1 inhibitors: In silico, synthesis, and in vitro studies.Archiv der Pharmazie · 2024Article
- Article
- Therapeutic Landscape of FOXM1 in Triple-Negative Breast Cancer and Aggressive Solid Cancers.Cancers · 2024Review
- The Importance of Stereochemistry in 5-HTACS chemical neuroscience · 2024Article
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- A drug repurposing study identifies novel FOXM1 inhibitors with in vitro activity against breast cancer cells.Medical oncology (Northwood, London, England) · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundTriple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with poor prognosis and shorter survival due to significant genetic heterogeneity, drug resistance and lack of effective targeted therapeutics. Therefore, novel molecular targets and therapeutic strategies are needed to improve patient survival. Serotonin (5-hydroxytryptamine, 5-HT) has been shown to induce growth stimulatory effects in breast cancer. However, the molecular mechanisms by which 5-HT exerts its oncogenic effects in TNBC still are not well understood.
methodsNormal breast epithelium (MCF10A) and two TNBC cells (MDA-MB-231, BT-546) and MCF-7 cells (ER +) were used to investigate effects of 5-HT7 receptor. Small interfering RNA (siRNA)-based knockdown and metergoline (5-HT7 antagonist) were used to inhibit the activity of 5-HT7. Cell proliferation and colony formation were evaluated using MTS cell viability and colony formation assays, respectively. Western blotting was used to investigate 5-HT7, FOXM1 and its downstream targets protein expressions.
resultsWe demonstrated that 5-HT induces cell proliferation of TNBC cells and expression of 5-HT7 receptor and FOXM1 oncogenic transcription factor. We found that expression of 5-HT7 receptor is up-regulated in TNBC cells and higher 5-HT7 receptor expression is associated with poor patient prognosis and shorter patient survival. Genetic and pharmacological inhibition of 5-HT7 receptor by siRNA and metergoline, respectively, suppressed TNBC cell proliferation and FOXM1 and its downstream mediators, including eEF2-Kinase (eEF2K) and cyclin-D1.
conclusionOur findings suggest for the first time that the 5-HT7 receptor promotes FOXM1, eEF2K and cyclin D1 signaling to support TNBC cell proliferation; thus, inhibition of 5-HT7 receptor/FOXM1 signaling may be used as a potential therapeutic strategy for targeting TNBC. 5-HT induces cell proliferation of TNBC cells through 5-HT7 receptor signaling. Also, genetic and pharmacological inhibition of 5-HT7 by RNAi (siRNA) and metergoline HTR7 antagonist, respectively inhibits FOXM1 oncogenic transcription factor and suppresses TNBC cell proliferation.
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