ArticleNeuro-oncology2023
Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- KIF14 silencing suppresses cell proliferation and enhances chemosensitivity by modulating 53BP1 nucleocytoplasmic shuttling in non-WNT/non-SHH medulloblastoma.Cell death discovery · 2026Article
- Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma.NAR cancer · 2025Article
- SLFN11, far from being limited to responding to cancer DNA damage.Clinical and experimental medicine · 2025Review
- From predictive biomarker to therapeutic target: the dual role of SLFN11 in chemotherapy sensitivity.Cancer chemotherapy and pharmacology · 2025Review
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.Molecular cell · 2025Article
- Article
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- The crucial role of single-stranded DNA binding in enhancing sensitivity to DNA-damaging agents for Schlafen 11 and Schlafen 13.iScience · 2023Article
- Schlafen 11 (SLFN11) Kills Cancer Cells Undergoing Unscheduled Re-replication.Molecular cancer therapeutics · 2023Article
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Authors and funding
40 authors at 12 institutions in 3 countries.
Funding
Abstract
backgroundIntensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma.
methodsSLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo.
resultsHigh SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells.
conclusionsHigh SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.
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