ArticleOncogene2018
EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.International journal of molecular sciences · 2024Pooled it
- Deacetylase inhibitors CM-444 and CM-1758 enhance chemotherapy response in AML via ALOX5.British journal of haematology · 2026Article
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- Diagnosis of early-stage non-small cell lung cancer using DNA methylation in tissue and plasma.Genes & diseases · 2025Article
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Immunohistochemical determination of the expression of Eph receptors in lipid-rich variation of experimental rat mammary carcinomas.Journal of molecular histology · 2025Article
- Development of a novel anti-erythropoietin-producing hepatocellular receptor B6 monoclonal antibody EbBiochemistry and biophysics reports · 2025Article
- Establishing a prognostic model with immune-related genes and investigating EPHB6 expression pattern in breast cancer.Scientific reports · 2025Article
- Co-clustering of EphB6 and ephrinB1 in trans restrains cancer cell invasion.Communications biology · 2024Article
- Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size.Molecular biology reports · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- A functional role of Ephrin type-B receptor 6 (EPHB6) in T-cell acute lymphoblastic leukemia.Biomarker research · 2023Article
- Synthesis and Development of Highly Selective Pyrrolo[2,3-Journal of medicinal chemistry · 2023Article
- Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.Frontiers in oncology · 2023Article
- EPHA2, EPHA4, and EPHA7 Expression in Triple-Negative Breast Cancer.Diagnostics (Basel, Switzerland) · 2022Article
- Fate decisions of breast cancer stem cells in cancer progression.Frontiers in oncology · 2022Review
- Ephrin Receptors (Ephs) Expression in Thymic Epithelial Tumors: Prognostic Implications and Future Therapeutic Approaches.Diagnostics (Basel, Switzerland) · 2021Article
- The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs.The Biochemical journal · 2021Article
- The EphB6 Receptor: Kinase-Dead but Very Much Alive.International journal of molecular sciences · 2021Review
- In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy.Nature communications · 2021Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.
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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.