Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- In utero exposure to diethylstilbestrol and blood DNA methylation in adult women: Results from a meta-analysis of two cohort studies.Environmental research · 2023Pooled it
- Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.Nature communications · 2019Pooled it
- Simvastatin modulates estrogen signaling in uterine leiomyoma via regulating receptor palmitoylation, trafficking and degradation.Pharmacological research · 2021Trial
- Molecular insights into uterine fibroids: crosstalk between SHH and Wnt pathways, DNA methylation, and miRNAs regulation.Molecular genetics and genomics : MGG · 2026Article
- Review
- Vitamin D and Uterine Fibroids: Insights into Pathophysiology and Therapeutic Potential.Endocrine reviews · 2026Review
- Wnt11 mediates fibroblast-smooth muscle cell interaction to promote neurogenic bladder fibrosis in rats.Communications biology · 2026Article
- Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation.Current medicinal chemistry · 2026Article
- Stem cell activation in organ culture reveals novel transcriptional programs underlying metabolic, fibrotic, vascular, and immune dysregulation in uterine leiomyomas.Frontiers in cell and developmental biology · 2026Article
- Mechanical Stiffness Influences the Response of Human Uterine Fibroid Cells to Hormonal Treatments.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Plasma Proteome-Wide Mendelian Randomization with Multi-Layer Triangulation Identifies Druggable Targets for Uterine Leiomyoma.International journal of women's health · 2026Article
- The Potential of Vitamin D and Epigallocatechin Gallate (EGCG) for the Treatment of Uterine Fibroids: Evidence From In Vitro to Clinical Studies.Molecular nutrition & food research · 2025Review
- Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights.Genes · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Review
- A systems-based approach to uterine fibroids identifies differential splicing associated with abnormal uterine bleeding.Communications medicine · 2025Article
- The influence of uterine leiomyomatosis on the onset of psoriasis: a nationwide population-based study of 2.5 million Korean females.BMC women's health · 2025Article
- Serum vitamin D as a novel biomarker for asymptomatic uterine fibroids: re-evaluating the risk threshold for incident fibroid development.Frontiers in global women's health · 2025Article
- Risk factors associated with pregnancy outcomes in patients with recurrent pregnancy loss after treatment.BMC pregnancy and childbirth · 2024Article
- Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.Oxygen (Basel, Switzerland) · 2024Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
Uterine leiomyomas are extremely common estrogen and progesterone-dependent tumors of the myometrium and cause irregular uterine bleeding, severe anemia, and recurrent pregnancy loss in 15-30% of reproductive-age women. Each leiomyoma is thought to arise from a single mutated myometrial smooth muscle stem cell. Leiomyoma side-population (LMSP) cells comprising 1% of all tumor cells and displaying tumor-initiating stem cell characteristics are essential for estrogen- and progesterone-dependent in vivo growth of tumors, although they have remarkably lower estrogen/progesterone receptor levels than mature myometrial or leiomyoma cells. However, how estrogen/progesterone regulates the growth of LMSP cells via mature neighboring cells is unknown. Here, we demonstrate a critical paracrine role of the wingless-type (WNT)/β-catenin pathway in estrogen/progesterone-dependent tumorigenesis, involving LMSP and differentiated myometrial or leiomyoma cells. Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues. In LMSP cells cocultured with mature myometrial cells, estrogen-progesterone selectively induced nuclear translocation of β-catenin and induced transcriptional activity of its heterodimeric partner T-cell factor and their target gene AXIN2, leading to the proliferation of LMSP cells. This effect could be blocked by a WNT antagonist. Ectopic expression of inhibitor of β-catenin and T-cell factor 4 in LMSP cells, but not in mature leiomyoma cells, blocked the estrogen/progesterone-dependent growth of human tumors in vivo. We uncovered a paracrine role of the WNT/β-catenin pathway that enables mature myometrial or leiomyoma cells to send mitogenic signals to neighboring tissue stem cells in response to estrogen and progesterone, leading to the growth of uterine leiomyomas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.