ArticleOncogene2016
Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
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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.
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Who cites it
42 citing papers in PubMed, 53 citations in OpenAlex.
- TAK1 is a key regulator of oncogenic signaling and differentiation blockade in rhabdomyosarcoma.Oncogene · 2026Article
- Towards directed therapy for fusion-positive rhabdomyosarcoma.Pharmacology & therapeutics · 2025Review
- TAK1 is a key regulator of oncogenic signaling and differentiation blockade in rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2025Article
- Transdifferentiation of endothelial progenitor cells into rhabdomyosarcoma defined by hedgehog signaling competence.Cell reports · 2025Article
- Wnt/β-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment.Children (Basel, Switzerland) · 2024Review
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Article
- Targeting the Hedgehog Pathway in Rhabdomyosarcoma.Cancers · 2023Review
- Review
- Article
- Toward a Personalized Therapy in Soft-Tissue Sarcomas: State of the Art and Future Directions.Cancers · 2021Review
- A method to culture human alveolar rhabdomyosarcoma cell lines as rhabdospheres demonstrates an enrichment in stemness and Notch signaling.Biology open · 2021Article
- Article
- Hedgehog/GLI1 signaling pathway regulates the resistance to cisplatin in human osteosarcoma.Journal of Cancer · 2021Article
- Article
- EHMT2 epigenetically suppresses Wnt signaling and is a potential target in embryonal rhabdomyosarcoma.eLife · 2020Article
- Cancer Stem Cells in Soft-Tissue Sarcomas.Cells · 2020Review
- Co-inhibition of BET proteins and PI3Kα triggers mitochondrial apoptosis in rhabdomyosarcoma cells.Oncogene · 2020Article
- Sonic Hedgehog Protein is Frequently Up-Regulated in Pancreatic Cancer Compared to Colorectal Cancer.Pathology oncology research : POR · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current treatment regimens for rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer, rely on conventional chemotherapy, and although they show clinical benefit, there is a significant risk of adverse side effects and secondary tumors later in life. Therefore, identifying and targeting sub-populations with higher tumorigenic potential and self-renewing capacity would offer improved patient management strategies. Hedgehog signaling has been linked to the development of embryonal RMS (ERMS) through mouse genetics and rare human syndromes. However, activating mutations in this pathway in sporadic RMS are rare and therefore the contribution of hedgehog signaling to oncogenesis remains unclear. Here, we show by genetic loss- and gain-of-function experiments and the use of clinically relevant small molecule modulators that hedgehog signaling is important for controlling self-renewal of a subpopulation of RMS cells in vitro and tumor initiation in vivo. In addition, hedgehog activity altered chemoresistance, motility and differentiation status. The core stem cell gene NANOG was determined to be important for ERMS self-renewal, possibly acting downstream of hedgehog signaling. Crucially, evaluating the presence of a subpopulation of tumor-propagating cells in patient biopsies identified by GLI1 and NANOG expression had prognostic significance. Hence, this work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers.
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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.