ArticleThe Journal of clinical investigation2015
MEL-18 loss mediates estrogen receptor-α downregulation and hormone independence.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- New Insights into TFEB SUMOylation and Its Role in Lipid Metabolism and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- The role of C1orf50 in breast cancer progression and prognosis.Breast cancer (Tokyo, Japan) · 2025Article
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- The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.International journal of molecular sciences · 2022Review
- Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer.Biomedicines · 2022Review
- Polycomb subunitFrontiers in cell and developmental biology · 2022Article
- Review
- Epigenetic mechanisms in breast cancer therapy and resistance.Nature communications · 2021Review
- CD63Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Article
- SUMO proteins in the cardiovascular system: friend or foe?Journal of biomedical science · 2020Review
- Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer.Science advances · 2020Article
- Epigenetic silencing of SALL2 confers tamoxifen resistance in breast cancer.EMBO molecular medicine · 2019Article
- CDK12 drives breast tumor initiation and trastuzumab resistance via WNT and IRS1-ErbB-PI3K signaling.EMBO reports · 2019Article
- Polycomb Assemblies Multitask to Regulate Transcription.Epigenomes · 2019Review
- Review
- Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms.Nature communications · 2018Article
- Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential.Cell death and differentiation · 2018Article
- Bone metastasis pattern in initial metastatic breast cancer: a population-based study.Cancer management and research · 2018Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor-α (ER-α, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-α-positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-α and the progesterone receptor (PR), MEL-18 overexpression restored ER-α expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer.
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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.