ArticleCancer research2013
Critical role of STAT3 in IL-6-mediated drug resistance in human neuroblastoma.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 125 citations in OpenAlex.
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.Investigative ophthalmology & visual science · 2026Review
- Antibody-Drug Conjugates Targeting Resistance-Associated Signaling Pathways: Recent Advances and Future Perspectives.International journal of molecular sciences · 2026Review
- Tumor Microenvironment in Neuroblastoma and Immunotherapeutic Approaches: Towards More Effective Treatment.Cancers · 2026Review
- Volumetric mechanoplasticity couples melanoma drug tolerance to susceptibility to CD8bioRxiv : the preprint server for biology · 2026Article
- TFF3 sensitizes cervical carcinoma cells to cisplatin toxicity by binding to IGF2R.Cancer gene therapy · 2026Article
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Integrated single-cell and bulk RNA sequencing analysis establishes a cancer associated fibroblast-related signature for predicting prognosis and therapeutic responses in neuroblastoma.Discover oncology · 2025Article
- The Diverse Function of IL-6 in Biological Processes and the Advancement of Cancer.Immune network · 2025Review
- Nuclear factor-κB activation by transforming growth factor-β1 drives tumour microenvironment-mediated drug resistance in neuroblastoma.British journal of cancer · 2024Article
- Review
- Pediatric Solid Cancers: Dissecting the Tumor Microenvironment to Improve the Results of Clinical Immunotherapy.International journal of molecular sciences · 2024Review
- TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.BMC molecular and cell biology · 2024Article
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
- A phase 1 study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors.Pediatric blood & cancer · 2023Article
- Review
- Interaction between tumor cell TNFR2 and monocyte membrane-bound TNF-α triggers tumorigenic inflammation in neuroblastoma.Journal for immunotherapy of cancer · 2023Article
- Therapy resistance in neuroblastoma: Mechanisms and reversal strategies.Frontiers in pharmacology · 2023Review
- The covert symphony: cellular and molecular accomplices in breast cancer metastasis.Frontiers in cell and developmental biology · 2023Review
- Diclofenac Sensitizes Signet Ring Cell Gastric Carcinoma Cells to Cisplatin by Activating Autophagy and Inhibition of Survival Signal Pathways.International journal of molecular sciences · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Drug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R). Treatment of neuroblastoma cells with IL-6 protected them from drug-induced apoptosis in a STAT3-dependent manner because the protective effect of IL-6 was abrogated in the presence of a STAT3 inhibitor and upon STAT3 knockdown. STAT3 was necessary for the upregulation of several survival factors such as survivin (BIRC5) and Bcl-xL (BCL2L1) when cells were exposed to IL-6. Importantly, IL-6-mediated STAT3 activation was enhanced by sIL-6R produced by human monocytes, pointing to an important function of monocytes in promoting IL-6-mediated EMDR. Our data also point to the presence of reciprocal activation of STAT3 between tumor cells and bone marrow stromal cells including not only monocytes but also regulatory T cells (Treg) and nonmyeloid stromal cells. Thus, the data identify an IL-6/sIL-6R/STAT3 interactive pathway between neuroblastoma cells and their microenvironment that contributes to drug resistance.
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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.