ArticleProceedings of the National Academy of Sciences of the United States of America2014
PDGFRβ reverses EphB4 signaling in alveolar rhabdomyosarcoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 40 citations in OpenAlex.
- Identification of EPHB4 as a potential causal gene and therapeutic target for endometriosis using Mendelian randomization.Hereditas · 2025Article
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- MAPK-targeted therapies in non-gastrointestinal stromal tumor soft tissue sarcomas: current landscape and future directions.Frontiers in oncology · 2025Review
- Trial in progress: phase I study of non-viral gene-modified CAR-T cell therapy for malignant solid tumors expressing EPHB4 receptor (CARTiEr).Frontiers in oncology · 2025Article
- The Clinical Relevance of the EPH/Ephrin Signaling Pathway in Pediatric Solid and Hematologic Malignancies.International journal of molecular sciences · 2024Review
- Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration.BMC cancer · 2024Article
- Designing molecules: directing stem cell differentiation.Frontiers in bioengineering and biotechnology · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- The EPH/Ephrin System in Bone and Soft Tissue Sarcomas' Pathogenesis and Therapy: New Advancements and a Literature Review.International journal of molecular sciences · 2022Review
- FGF7-FGFR2 autocrine signaling increases growth and chemoresistance of fusion-positive rhabdomyosarcomas.Molecular oncology · 2022Article
- Review
- Preclinical therapeutics ex ovo quail eggs as a biomimetic automation-ready xenograft platform.Scientific reports · 2021Article
- Review
- Article
- Interleukin-4 Receptor Inhibition Targeting Metastasis Independent of Macrophages.Molecular cancer therapeutics · 2021Article
- Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma.Molecular therapy oncolytics · 2021Article
- The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.Expert review of anticancer therapy · 2019Review
- Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma.BMC cancer · 2019Article
- Exogenous expression of the glycosyltransferase LARGE1 restores α-dystroglycan matriglycan and laminin binding in rhabdomyosarcoma.Skeletal muscle · 2019Article
- Pannexin 1 inhibits rhabdomyosarcoma progression through a mechanism independent of its canonical channel function.Oncogenesis · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alveolar rhabdomyosarcoma (aRMS) is an aggressive myogenic childhood malignancy, not infrequently presenting as incurable metastatic disease. To identify therapeutic targets, we performed an unbiased tyrosine kinome RNA interference screen in primary cell cultures from a genetically engineered, conditional mouse model of aRMS. We identified ephrin receptor B4 (EphB4) as a target that is widely expressed in human aRMS and that portends a poor clinical outcome in an expression level-dependent manner. We also uncovered cross-talk of this ephrin receptor with another receptor tyrosine kinase, PDGFRβ, which facilitates PDGF ligand-dependent, ephrin ligand-independent activation of EphB4 converging on the Akt and Erk1/2 pathways. Conversely, EphB4 activation by its cognate ligand, EphrinB2, did not stimulate PDGFRβ; instead, apoptosis was paradoxically induced. Finally, we showed that small-molecule inhibition of both PDGFRβ and EphB4 by dasatinib resulted in a significant decrease in tumor cell viability in vitro, as well as decreased tumor growth rate and significantly prolonged survival in vivo. To our knowledge, these results are the first to identify EphB4 and its cross-talk with PDGFRβ as unexpected vital determinants of tumor cell survival in aRMS, with EphB4 at the crux of a bivalent signaling node that is either mitogenic or proapoptotic.
Indexed as
Identifiers
What OpenQuestion holds
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.