ArticleCancer biology & medicine2019
Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways.
Article in Cancer biology & medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- Effects of metformin on transcriptomic and metabolomic profiles in breast cancer survivors enrolled in the randomized placebo-controlled MetBreCS trial.Scientific reports · 2025Trial
- When Estrogen Signaling Refuses to Die: Receptor Rewiring, Compartmentalization, and Endocrine Plasticity in Gynecological Cancers.International journal of molecular sciences · 2026Review
- Article
- Weight-centric prevention of cancer.Obesity pillars · 2024Review
- Comparison of the gene expression profiles of endometrial and trophoblastic cells in women with recurrent miscarriage: A bioinformatics approach.International journal of reproductive biomedicine · 2024Article
- Endogenous estrogen metabolites as oxidative stress mediators and endometrial cancer biomarkers.Cell communication and signaling : CCS · 2024Review
- A mixture ofHeliyon · 2024Article
- Diverging likelihood of colon and rectal cancer in Yogyakarta, Indonesia: A cross sectional study.PloS one · 2024Article
- Roles of estrogen receptor α in endometrial carcinoma (Review).Oncology letters · 2023Review
- Unveiling the Role of Hormonal Imbalance in Breast Cancer Development: A Comprehensive Review.Cureus · 2023Review
- Glucose metabolic reprogramming and its therapeutic potential in obesity-associated endometrial cancer.Journal of translational medicine · 2023Review
- The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions.Frontiers in endocrinology · 2023Review
- Estrogen receptor 1 inhibits the progression of hepatocellular carcinoma via positively regulating lncRNA maternally expressed gene 3 under high glucose conditions.Journal of gastrointestinal oncology · 2022Article
- Endometrial Expression of Insulin Signaling Pathway Genes in Pregnancy Leading to Abortion under 20 Weeks in Infertile Women: A Case-Control Study.International journal of fertility & sterility · 2022Article
- Exploring the mechanism and experimental verification of puerarin in the treatment of endometrial carcinoma based on network pharmacology and bioinformatics analysis.BMC complementary medicine and therapies · 2022Article
- Estrogen Receptors-Mediated Apoptosis in Hormone-Dependent Cancers.International journal of molecular sciences · 2022Review
- The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer.Frontiers in surgery · 2022Review
- Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer-associated fibroblasts.Clinical and translational medicine · 2021Article
- p38β - MAPK11 and its role in female cancers.Journal of ovarian research · 2021Review
- PRMT5 promotes progression of endometrioid adenocarcinoma via ERα and cell cycle signaling pathways.The journal of pathology. Clinical research · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDespite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma (EC) has not been analyzed yet.
methodsHere, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth
resultsCompared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation, cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.
conclusionsEstrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α, promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.
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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.