ArticleCell death & disease2020
Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Immune Cell Therapy Promises More Effective Cure for Medulloblastoma.Journal of personalized medicine · 2026Review
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- IL-6R blockade with tocilizumab disrupts pericyte- and tumor cell-driven IL-6/STAT3 signaling, enhancing docetaxel efficacy in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Importance of STAT3 signaling in preeclampsia (Review).International journal of molecular medicine · 2025Review
- CTSL Promotes Autophagy in Laryngeal Cancer Through the IL6-JAK-STAT3 Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by RNA-Seq.Antioxidants (Basel, Switzerland) · 2025Article
- Exercise-mediated IL-6 downstream effects modulate brain pathology-can exercise training protocols influence the downstream effects?Frontiers in neurology · 2025Review
- Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.Translational oncology · 2024Review
- Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies.Cancers · 2024Review
- Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.Cancers · 2024Review
- Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.PLoS pathogens · 2024Article
- IL-6 promotes tumor growth through immune evasion but is dispensable for cachexia.EMBO reports · 2024Article
- Tumor suppressor role of the complement inhibitor CSMD1 and its role in TNF-induced neuroinflammation in gliomas.Journal of experimental & clinical cancer research : CR · 2024Article
- Tumor suppressor p53 mediates interleukin-6 expression to enable cancer cell evasion of genotoxic stress.Cell death discovery · 2023Article
- Sonic hedgehog signaling: Alternative splicing and pathogenic role in medulloblastoma.Genes & diseases · 2023Review
- Action mechanism of snake venom l-amino acid oxidase and its double-edged sword effect on cancer treatment: Role of pannexin 1-mediated interleukin-6 expression.Redox biology · 2023Article
- Review
- Article
- Cellular immunotherapy for medulloblastoma.Neuro-oncology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medulloblastoma (MB) is a high-grade pediatric brain malignancy that originates from neuronal precursors located in the posterior cranial fossa. In this study, we evaluated the role of STAT3 and IL-6 in a tumor microenvironment mediated drug resistance in human MBs. We established that the Group 3 MB cell line, Med8A, is chemosensitive (hence Med8A-S), and this is correlated with a basal low phosphorylated state of STAT3, while treatment with IL-6 induced robust increases in pY705-STAT3. Via incremental selection with vincristine, we derived the stably chemoresistant variant, Med8A-R, that exhibited multi-drug resistance, enhanced IL-6 induced pY705-STAT3 levels, and increased IL6R expression. Consequently, abrogation of STAT3 or IL6R expression in Med8A-R led to restored chemosensitivity to vincristine, highlighting a prominent role for canonical IL-6/STAT3 signaling in acquired drug resistance. Furthermore, Med8A-S subjected to conditioning exposure with IL-6, termed Med8A-IL6+ cells, exhibited enhanced vincristine resistance, increased expression of pY705-STAT3 and IL6R, and increased secretion of IL-6. When cocultured with Med8A-IL6+ cells, Med8A-S cells exhibited increased pY705-STAT3 and increased IL-6 secretion, suggesting a cytokine feedback loop responsible for amplifying STAT3 activity. Similar IL-6 induced phenomena were also observed in the Group 3 MB cell lines, D283 and D341, including increased pY705-STAT3, drug resistance, IL-6 secretion and IL6R expression. Our study unveiled autocrine IL-6 as a promoter of STAT3 signaling in development of drug resistance, and suggests therapeutic benefits for targeting the IL-6/STAT3 signaling axis in Group 3 MBs.
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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.