ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
IL-4R drives dedifferentiation, mitogenesis, and metastasis in rhabdomyosarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Association of the interleukin-4Rα rs1801275 and rs1805015 polymorphisms with glioma risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Context-Dependent Survival Associations Between Interleukin-13 Expression and Immunotherapy in Advanced Solid Tumors.ImmunoTargets and therapy · 2026Article
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- Article
- Developmental and therapeutic implications of IL4ra expression for rhabdomyosarcoma.Transgenic research · 2024Article
- Protein-modified nanomaterials: emerging trends in skin wound healing.Discover nano · 2023Review
- Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy.Cancers · 2021Review
- Design considerations of an IL13Rα2 antibody-drug conjugate for diffuse intrinsic pontine glioma.Acta neuropathologica communications · 2021Article
- Interleukin-4 Receptor Inhibition Targeting Metastasis Independent of Macrophages.Molecular cancer therapeutics · 2021Article
- Expression of IL4Rα and IL13Rα1 are associated with poor prognosis of soft-tissue sarcoma of the extremities, superficial trunk, and retroperitoneum.Diagnostic pathology · 2021Article
- Defining the Extracellular Matrix of Rhabdomyosarcoma.Frontiers in oncology · 2021Article
- KDM3A/Ets1 epigenetic axis contributes to PAX3/FOXO1-driven and independent disease-promoting gene expression in fusion-positive Rhabdomyosarcoma.Molecular oncology · 2020Article
- Interleukin-4 Signaling Plays a Major Role in Urogenital Schistosomiasis-Associated Bladder Pathogenesis.Infection and immunity · 2020Article
- Downregulation of POFUT1 Impairs Secondary Myogenic Fusion Through a Reduced NFATc2/IL-4 Signaling Pathway.International journal of molecular sciences · 2019Article
- The Transcriptional Coactivator TAZ Is a Potent Mediator of Alveolar Rhabdomyosarcoma Tumorigenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia.Cancer research · 2018Article
- Acquisition of an oncogenic fusion protein is sufficient to globally alter the landscape of miRNA expression to inhibit myogenic differentiation.Oncotarget · 2017Article
- Interleukin-4 and interleukin-13 increase NADPH oxidase 1-related proliferation of human colon cancer cells.Oncotarget · 2017Article
- Obesity Does Not Exacerbate the Protumorigenic Systemic Environment in Sarcoma Subjects.ImmunoHorizons · 2017Article
- Blocking Interleukin-4 Receptor α Using Polyethylene Glycol Functionalized Superparamagnetic Iron Oxide Nanocarriers to Inhibit Breast Cancer Cell Proliferation.Cancer research and treatment · 2017Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
purposeRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. The alveolar subtype of rhabdomyosarcoma (ARMS) is a paradigm for refractory and incurable solid tumors because more than half of the children at diagnosis have either regional lymph node or distant metastases. These studies follow our previous observation that Interleukin-4 receptor α (IL-4Rα) is upregulated in both human and murine ARMS, and that the IL-4R signaling pathway may be a target for abrogating tumor progression. EXPERIMENTAL
designBy in vitro biochemical and cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of IL-4 and IL-13 in IL-4R-mediated mitogenesis, myodifferentiation, and tumor progression.
resultsIL-4 and IL-13 ligands accelerated tumor cell growth and activated STAT6, Akt, or MAPK signaling pathways in the human RMS cell lines, RD and Rh30, as well as in mouse primary ARMS cell cultures. IL-4 and IL-13 treatment also decreased protein expression of myogenic differentiation factors MyoD and Myogenin, indicating a loss of muscle differentiation. Using a genetically engineered mouse model of ARMS, we have shown that inhibition of IL-4R signaling pathway with a neutralizing antibody has a profound effect on the frequency of lymph node and pulmonary metastases, resulting in significant survival extension in vivo.
conclusionsOur results indicate that an IL-4R-dependent signaling pathway regulates tumor cell progression in RMS, and inhibition of this pathway could be a promising adjuvant therapeutic approach.
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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.