ArticleThe Journal of clinical investigation2014
A phosphotyrosine switch determines the antitumor activity of ERβ.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Targeting Subcellular Organelles in Breast Cancer with Enzyme Induced Self-Assembly: Stimulated Response with Eyes-Absence Enzymes (EYA).Molecular pharmaceutics · 2025Article
- Estrogen Signals through ERβ in Breast Cancer; What We Have Learned since the Discovery of the Receptor.Receptors (Basel, Switzerland) · 2024Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation.Nature communications · 2024Article
- The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51.Nucleic acids research · 2024Article
- In Vitro Phosphatase Assays for the Eya2 Tyrosine Phosphatase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression.Neuro-oncology · 2023Article
- Preclinical Development of Brain Permeable ERβ Agonist for the Treatment of Glioblastoma.Molecular cancer therapeutics · 2023Article
- Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.iScience · 2023Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.Nucleic acids research · 2022Article
- Article
- Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe.The Journal of experimental medicine · 2021Article
- Absolute Quantification of Phosphorylated ERβ Amino Acids in the Hippocampus of Women and in A Rat Model of Menopause.Endocrinology · 2021Article
- The Eyes Absent proteins in development and in developmental disorders.Biochemical Society transactions · 2021Review
- The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases.International journal of molecular sciences · 2021Review
- A Phosphotyrosine Switch in Estrogen Receptor β Is Required for Mouse Ovarian Function.Frontiers in cell and developmental biology · 2021Article
- Estrogen receptor beta signaling in CD8Journal for immunotherapy of cancer · 2021Article
- The multi-functional eyes absent proteins.Critical reviews in biochemistry and molecular biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
Abstract
Estrogen receptors ERα and ERβ share considerable sequence homology yet exert opposite effects on breast cancer cell proliferation. While the proliferative role of ERα in breast tumors is well characterized, it is not clear whether the antitumor activity of ERβ can be mobilized in breast cancer cells. Here, we have shown that phosphorylation of a tyrosine residue (Y36) present in ERβ, but not in ERα, dictates ERβ-specific activation of transcription and is required for ERβ-dependent inhibition of cancer cell growth in culture and in murine xenografts. Additionally, the c-ABL tyrosine kinase and EYA2 phosphatase directly and diametrically controlled the phosphorylation status of Y36 and subsequent ERβ function. A nonphosphorylatable, transcriptionally active ERβ mutant retained antitumor activity but circumvented control by upstream regulators. Phosphorylation of Y36 was required for ERβ-mediated coactivator recruitment to ERβ target promoters. In human breast cancer samples, elevated phosphorylation of Y36 in ERβ correlated with high levels of c-ABL but low EYA2 levels. Furthermore, compared with total ERβ, the presence of phosphorylated Y36-specific ERβ was strongly associated with both disease-free and overall survival in patients with stage II and III disease. Together, these data identify a signaling circuitry that regulates ERβ-specific antitumor activity and has potential as both a prognostic tool and a molecular target for cancer therapy.
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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.