ArticleOncotarget2016
Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Klotho in Cancer: Potential Diagnostic and Prognostic Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Molecular Landscape of Pelvic Organ Prolapse Provides Insights into Disease Etiology.International journal of molecular sciences · 2023Article
- The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC.International journal of molecular sciences · 2022Article
- Intersections of endocrine pathways and the epithelial mesenchymal transition in endometrial cancer.Frontiers in oncology · 2022Review
- Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.Reproductive biology and endocrinology : RB&E · 2021Article
- Serum β-klotho is a potential biomarker in the prediction of clinical outcomes among patients with NSCLC.Journal of thoracic disease · 2021Article
- βKlotho Inhibits Cell Proliferation by Downregulating ELK4 and Predicts Favorable Prognosis in Prostate Cancer.Cancer management and research · 2021Article
- βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling.American journal of cancer research · 2021Article
- Article
- Medroxyprogesterone Reverses Tolerable Dose Metformin-Induced Inhibition of Invasion via Matrix Metallopeptidase-9 and Transforming Growth Factor-β1 in KLE Endometrial Cancer Cells.Journal of clinical medicine · 2020Article
- Metformin regulation of progesterone receptor isoform-B expression in human endometrial cancer cells is glucose-dependent.Oncology letters · 2020Article
- Review
- N-acetyl-seryl-aspartyl-lysyl-proline is a valuable endogenous antifibrotic peptide for kidney fibrosis in diabetes: An update and translational aspects.Journal of diabetes investigation · 2020Review
- Soluble guanylyl cyclase α1 subunit is a key mediator of proliferation, survival, and migration in ECC-1 and HeLa cell lines.Scientific reports · 2019Article
- βklotho is essential for the anti-endothelial mesenchymal transition effects of N-acetyl-seryl-aspartyl-lysyl-proline.FEBS open bio · 2019Article
- NUMB knockdown enhanced the anti-tumor role of cisplatin on ovarian cancer cells by inhibiting cell proliferation and epithelial-mesenchymal transition.Translational cancer research · 2019Article
- βKlotho inhibits androgen/androgen receptor‑associated epithelial‑mesenchymal transition in prostate cancer through inactivation of ERK1/2 signaling.Oncology reports · 2018Article
- Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells.Reproductive biology and endocrinology : RB&E · 2018Article
- Crucial microRNAs and genes in metformin's anti-pancreatic cancer effect explored by microRNA-mRNA integrated analysis.Investigational new drugs · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.
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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.