ArticleMolecular endocrinology (Baltimore, Md.)2012
ERβ-mediated estradiol enhances epithelial mesenchymal transition of lung adenocarcinoma through increasing transcription of midkine.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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
34 citing papers in PubMed, 47 citations in OpenAlex.
- Midkine and pleiotrophin in glioma: From mechanistic insights to therapeutic potential.Neoplasia (New York, N.Y.) · 2026Review
- Coordinated changes in midkine expression and midkine-associated multiomic profile in glioma microenvironment.Scientific reports · 2025Article
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- Ugonin P mitigates osteolytic bone metastasis by suppressing MDK via upregulating miR-223-3p expression.International journal of biological sciences · 2025Article
- The estrogen response in fibroblasts promotes ovarian metastases of gastric cancer.Nature communications · 2024Article
- Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting.International journal of molecular sciences · 2023Review
- CAF-derived midkine promotes EMT and cisplatin resistance by upregulating lncRNA ST7-AS1 in gastric cancer.Molecular and cellular biochemistry · 2022Article
- Estrogen receptor beta promotes lung cancer invasion via increasing CXCR4 expression.Cell death & disease · 2022Article
- Increased serum concentrations of estrogen-induced growth factors Midkine and FGF2 in NF1 patients with plexiform neurofibroma.American journal of translational research · 2022Article
- Review
- H. sinensis mycelium inhibits epithelial-mesenchymal transition by inactivating the midkine pathway in pulmonary fibrosis.Frontiers of medicine · 2021Article
- Hormone gene signature guides a novel therapeutic opportunity to improve sensitivity to HER family inhibition in lung cancer.Translational lung cancer research · 2020Article
- Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.Oncogene · 2020Review
- Review
- Prognostic value of ESR2 expression on adjuvant chemotherapy in completely resected NSCLC.PloS one · 2020Article
- Article
- Effect of midkine on gemcitabine resistance in biliary tract cancer.International journal of molecular medicine · 2018Article
- Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies.International journal of molecular sciences · 2018Review
- High expression of ZEB1 in endometriosis and its role in 17β-estradiol-induced epithelial-mesenchymal transition.International journal of clinical and experimental pathology · 2018Article
- Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of lncRNA ANRIL in tumour cells.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) plays a specific role in the migration of tumor cells. Both estrogen and midkine (MK) have been thought to be important factors in promoting the progression of non-small-cell lung cancer (NSCLC) and can enhance EMT. Some evidence indicated the correlation between estradiol (E2) and MK, but the precise mechanism on their interreaction is unknown. Here, we try to clarify whether and how E2 regulates MK expression to promote EMT. We found that E2 increased MK mRNA expression in lung adenocarcinoma cells LTEP-a2 and A549 in a time-dependent manner. E2-induced MK expression was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and tamoxifen but not by phosphoinositide-3 kinase and MAPK inhibitors, suggesting a genomic mechanism of E2 on the regulation of MK transcription. Moreover, luciferase reporter and chromatin immunoprecipitation assays exhibited that E2 induced ERβ recruitment to the estrogen response element in the MK promoter. Small interfering RNA to ERα and ERβ revealed that ERβ mainly mediated E2-induced MK transcription. Interestingly, E2 enhanced MK expression in accordance with increase of EMT, whereas knockdown of MK could block EMT under E2 stimulation. Importantly, through analyzing lung adenocarcinoma tissues, there was indeed a correlation among levels of E2, MK, and EMT-related protein expression. Taken together, we reported a previously unrecognized mechanism on E2 in the regulation of MK expression and proved that MK plays a pivotal role in progression of E2-regulated EMT.
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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.