ArticleCancer research2011
SPARC stimulates neuronal differentiation of medulloblastoma cells via the Notch1/STAT3 pathway.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis.PloS one · 2016Pooled it
- Targeting SRC enhances differentiation and promotes multifaceted cell death mechanisms in recurrent group 3 medulloblastoma.Cell death & disease · 2026Article
- Molecular flexibility of hyaluronic acid has a profound effect on invasion of cancer cells.Royal Society open science · 2025Article
- SPARC Promotes Aerobic Glycolysis and 5-Fluorouracil Resistance in Colorectal Cancer Through the STAT3/HK2 Axis.Cancer medicine · 2025Article
- GP60 and SPARC as albumin receptors: key targeted sites for the delivery of antitumor drugs.Frontiers in pharmacology · 2024Review
- STAT3 in medulloblastoma: a key transcriptional regulator and potential therapeutic target.Molecular biology reports · 2022Review
- Tumour-derived substrate-adherent cells promote neuroblastoma survival through secreted trophic factors.Molecular oncology · 2021Article
- Enhanced Osteogenic Differentiation of Pluripotent Stem Cells via γ-Secretase Inhibition.International journal of molecular sciences · 2021Article
- IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2021Article
- The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation.Cellular & molecular biology letters · 2021Article
- SPARC overexpression alters microRNA expression profiles involved in tumor progression.Genes & cancer · 2017Article
- SPARC: As a prognostic biomarker in rectal cancer patients treated with chemo-radiotherapy.Cancer biomarkers : section A of Disease markers · 2017Article
- SPARC expression in gastric cancer predicts poor prognosis: Results from a clinical cohort, pooled analysis and GSEA assay.Oncotarget · 2016Article
- Notch: A multi-functional integrating system of microenvironmental signals.Developmental biology · 2016Review
- Review
- Notch signaling in cerebrovascular diseases (Review).Molecular medicine reports · 2016Review
- Oxytocin Increases Neurite Length and Expression of Cytoskeletal Proteins Associated with Neuronal Growth.Journal of molecular neuroscience : MN · 2016Article
- Amitriptyline improves motor function via enhanced neurotrophin signaling and mitochondrial functions in the murine N171-82Q Huntington disease model.The Journal of biological chemistry · 2015Article
- Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats.PloS one · 2015Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Secreted protein acidic and rich in cysteine (SPARC) participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we show that adenoviral-mediated overexpression of SPARC cDNA (Ad-DsRed-SP) elevated the expression of the neuronal markers NeuN, nestin, neurofilament, and MAP-2 in medulloblastoma cells and induced neuron-like differentiation. SPARC overexpression decreased STAT3 phosphorylation; constitutive expression of STAT3 reversed SPARC-mediated expression of neuronal markers. We also show that Notch signaling is suppressed in the presence of SPARC, as well as the Notch effector basic helix-loop-helix (bHLH) transcription factor hairy and enhancer of split 1 (HES1). Notch signaling was found to be responsible for the decreased STAT3 phosphorylation in response to SPARC expression. Furthermore, expression of SPARC decreased the production of interleukin 6 (IL-6) and supplemented IL-6-abrogated, SPARC-mediated suppression of Notch signaling and expression of neuronal markers. Immunohistochemical analysis of tumor sections from mice treated with Ad-DsRed-SP showed increased immunoreactivity for the neuronal markers and a decrease in Notch1 expression and phosphorylation of STAT3. Taken together, our results suggest that SPARC induces expression of neuronal markers in medulloblastoma cells through its inhibitory effect on IL-6-regulated suppression of Notch pathway-mediated STAT3 signaling, thus giving further support to the potential use of SPARC as a therapeutic candidate for medulloblastoma treatment. Findings show that SPARC-induced neuronal differentiation can sensitize medulloblastoma cells for therapy.
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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.