ArticleThe Journal of clinical investigation2018
Eya3 promotes breast tumor-associated immune suppression via threonine phosphatase-mediated PD-L1 upregulation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- NAT10-Mediated ac4C Modification of circANKRD12 Reprograms the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic and Pharmacologic Targeting of Eya3 in Macrophages Drives Anti-Tumor Immunity in Triple-Negative Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting Subcellular Organelles in Breast Cancer with Enzyme Induced Self-Assembly: Stimulated Response with Eyes-Absence Enzymes (EYA).Molecular pharmaceutics · 2025Article
- Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression.PLoS biology · 2025Review
- Beyond the Limit: MYC Mediates Tumor Immune Escape.Pharmaceuticals (Basel, Switzerland) · 2025Review
- EYA3 regulation of NF-κB and CCL2 suppresses cytotoxic NK cells in the premetastatic niche to promote TNBC metastasis.Science advances · 2025Article
- Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.International journal of biological sciences · 2025Article
- EYA3 promotes the tumorigenesis of gastric cancer through activation of the mTORC1 signaling pathway and inhibition of autophagy.Scientific reports · 2024Article
- Biochemical characterization of the Eya and PP2A-B55α interaction.The Journal of biological chemistry · 2024Article
- Establishment of glioma prognosis nomogram based on the function of meox1 in promoting the progression of cancer.Heliyon · 2024Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- RBFOX2 regulated EYA3 isoforms partner with SIX4 or ZBTB1 to control transcription during myogenesis.iScience · 2023Article
- The value of EYA1/3/4 in clear cell renal cell carcinoma: a study from multiple databases.Scientific reports · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- MYC Overexpression Drives Immune Evasion in Hepatocellular Carcinoma That Is Reversible through Restoration of Proinflammatory Macrophages.Cancer research · 2023Article
- Retinal determination gene networks: from biological functions to therapeutic strategies.Biomarker research · 2023Review
- Both a hypoxia-inducible EYA3 and a histone acetyltransferase p300 function as coactivators of SIX5 to mediate tumorigenesis and cancer progression.Annals of translational medicine · 2022Article
- Blockading a new NSCLC immunosuppressive target by pluripotent autologous tumor vaccines magnifies sequential immunotherapy.Bioactive materials · 2022Article
- A FBXO7/EYA2-SCFMolecular cell · 2022Article
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13 authors at 6 institutions in 3 countries.
Funding
Abstract
Eya proteins are critical developmental regulators that are highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs in many tumor types. In breast cancer, Eyas regulate tumor progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, Eyas harbor a separate threonine (Thr) phosphatase activity, which was previously implicated in innate immunity. Here we describe what we believe to be a novel role for Eya3 in mediating triple-negative breast cancer-associated immune suppression. Eya3 loss decreases tumor growth in immune-competent mice and is associated with increased numbers of infiltrated CD8+ T cells, which, when depleted, reverse the effects of Eya3 knockdown. Mechanistically, Eya3 utilizes its Thr phosphatase activity to dephosphorylate Myc at pT58, resulting in a stabilized form. We show that Myc is required for Eya3-mediated increases in PD-L1, and that rescue of PD-L1 in Eya3-knockdown cells restores tumor progression. Finally, we demonstrate that Eya3 significantly correlates with PD-L1 in human breast tumors, and that tumors expressing high levels of Eya3 have a decreased CD8+ T cell signature. Our data uncover a role for Eya3 in mediating tumor-associated immune suppression, and suggest that its inhibition may enhance checkpoint therapies.
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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.