ArticleFertility and sterility2020
Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function.
Article in Fertility and sterility, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Dysregulation of PI3K/AKT signaling pathway in uterine leiomyoma: paired tissue-specific in-situ analysis.Molecular biology reports · 2026Article
- Compressive force induces differential gene and protein expression in uterine fibroids.F&S science · 2025Article
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Review
- MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas.JCI insight · 2023Article
- Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas.International journal of molecular sciences · 2023Article
- Simvastatin inhibits stem cell proliferation in human leiomyoma via TGF-β3 and Wnt/β-Catenin pathways.Journal of cellular and molecular medicine · 2022Article
- Review
- WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cellsFrontiers in oncology · 2022Article
- Simvastatin Inhibits Wnt/β-Catenin Pathway in Uterine Leiomyoma.Endocrinology · 2021Article
- Spatial transcriptomics analysis of uterine gene expression in enhancer of zeste homolog 2 conditional knockout mice†.Biology of reproduction · 2021Article
- Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities.Molecular and cellular biochemistry · 2021Review
- Molecular and Cellular Insights into the Development of Uterine Fibroids.International journal of molecular sciences · 2021Review
- Uterine Stem Cells and Benign Gynecological Disorders: Role in Pathobiology and Therapeutic Implications.Stem cell reviews and reports · 2021Review
- Endometriosis and Uterine Fibroids (Leiomyomata): Comorbidity, Risks and Implications.Frontiers in reproductive health · 2021Review
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
objectiveTo investigate the functional interaction between the Wnt/β-catenin and protein kinase B (Akt) pathways in leiomyoma stem cells (LSC).
designLaboratory study.
settingResearch laboratory. PATIENT(S): Premenopausal women (n = 36; age range: 28 to 49 years) undergoing hysterectomy or myomectomy for leiomyoma. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression, protein phosphorylation, and cell proliferation. RESULT(S): Cells from human leiomyoma tissues were sorted by fluorescence-activated cell sorting (FACS) into three populations: LSC, intermediate cells (LIC), and differentiated cells (LDC) with the function of the Wnt/β-catenin and Akt signaling pathways in leiomyoma cells evaluated using real-time quantitative polymerase chain reaction and immunoblot analyses. The Wnt/β-catenin signaling pathway components were differentially expressed in each leiomyoma cell population. WNT4 was distinctly overexpressed in LIC, and its receptor FZD6 was primarily expressed in LSC. WNT4 stimulated Akt phosphorylation, activated β-catenin, and increased primary leiomyoma cell proliferation. These stimulatory effects were abolished by cotreatment with the Akt inhibitor, MK-2206. WNT4 up-regulated the expression of pro-proliferative genes, c-Myc and cyclin D1, specifically in LSC; this was also abrogated by Akt inhibition. CONCLUSION(S): Our data suggest that WNT4 regulates LSC proliferation via Akt-dependent β-catenin activation, representing a key step toward a better understanding of LSC regulation and potentially novel therapeutic targets.
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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.