ArticlePloS one2014
Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Glypican 3 as target therapy to prevent cell migration and proliferation in rhabdomyosarcoma.Scientific reports · 2025Article
- A SNAI2/CTCF Interaction is Required forMolecular and cellular biology · 2023Article
- Notch signaling in the pathogenesis, progression and identification of potential targets for cholangiocarcinoma (Review).Molecular and clinical oncology · 2022Review
- Genetics, epigenetics and redox homeostasis in rhabdomyosarcoma: Emerging targets and therapeutics.Redox biology · 2019Review
- The Role ofThe oncologist · 2018Review
- A Novel Notch-YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma.Molecular cancer research : MCR · 2017Article
- PAX7 is a required target for microRNA-206-induced differentiation of fusion-negative rhabdomyosarcoma.Cell death & disease · 2016Article
- Histone Deacetylase Inhibitors Antagonize Distinct Pathways to Suppress Tumorigenesis of Embryonal Rhabdomyosarcoma.PloS one · 2015Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rhabdomyosarcoma (RMS) is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.
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