ArticleNeoplasia (New York, N.Y.)2018
The STAT3 Target Gene TNFRSF1A Modulates the NF-κB Pathway in Breast Cancer Cells.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses 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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Role of STAT3 signaling pathway in breast cancer.Cell communication and signaling : CCS · 2020Pooled it
- STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019Pooled it
- Mapping malignant T-cell states and immune circuits in Sézary syndrome by single-cell analysis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Article
- M196R-TNFR2 and membrane TNFα down-regulate soluble TNFα-induced pro-metastatic functions in triple-negative breast cancer cells.Cancer cell international · 2026Article
- Integrated Study of Vancomycin-Induced Nephrotoxicity in the Context of Sepsis: Animal Models and Transcriptomics.Kidney360 · 2026Article
- NAT10-mediated acCellular & molecular biology letters · 2026Article
- Transcriptomic analysis of the physiological responses to injuries induced accompanying intracortical microelectrode implantation.Biomaterials · 2026Article
- Evidence for enhancer activity in intron 1 of TNFRSF1A using CRISPR/Cas9 in human induced pluripotent stem cell-derived macrophages.Scientific reports · 2025Article
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- Targeting inflammation in cancer therapy: from mechanistic insights to emerging therapeutic approaches.Journal of translational medicine · 2025Review
- The Roles of STAT3 and STAT5 in Breast Cancer.Cancers · 2025Review
- Abnormal expression of CDC25C in NSCLC is influenced by transcriptional and RNA N6‑methyladenosine‑mediated post‑transcriptional regulation.International journal of oncology · 2025Article
- Immunomodulatory Properties of Sweet Whey-Derived Peptides in THP-1 Macrophages.Molecules (Basel, Switzerland) · 2025Article
- Identification of PRKCQ-AS1 as a Keratinocyte-Derived Exosomal lncRNA That Promotes Th17 Differentiation and IL-17 secretion in Psoriasis Through Bioinformatics, Machine Learning Algorithms, and Cell Experiments.Journal of inflammation research · 2025Article
- Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation.Disease models & mechanisms · 2024Article
- Identification of modules and key genes associated with breast cancer subtypes through network analysis.Scientific reports · 2024Article
- Identification of Susceptibility Genes Underlying Bovine Respiratory Disease in Xinjiang Brown Cattle Based on DNA Methylation.International journal of molecular sciences · 2024Article
- First-in-human Phase I Trial of TPST-1120, an Inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors.Cancer research communications · 2024Article
- Identification of TNFRSF1A as a potential biomarker for osteosarcoma.Cancer biomarkers : section A of Disease markers · 2024Article
- Cancer and Alzheimer's Inverse Correlation: an Immunogenetic Analysis.Molecular neurobiology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor STAT3 is activated inappropriately in 70% of breast cancers, most commonly in triple negative breast cancer (TNBC). Although the transcriptional function of STAT3 is essential for tumorigenesis, the key target genes regulated by STAT3 in driving tumor pathogenesis have remained unclear. To identify critical STAT3 target genes, we treated TNBC cell lines with two different compounds that block STAT3 transcriptional function, pyrimethamine and PMPTP. We then performed gene expression analysis to identify genes whose expression is strongly down-regulated by both STAT3 inhibitors. Foremost among the down-regulated genes was TNFRSF1A, which encodes a transmembrane receptor for TNFα. We showed that STAT3 binds directly to a regulatory region within the TNFRSF1A gene, and that TNFRSF1A levels are dependent on STAT3 function in both constitutive and cytokine-induced models of STAT3 activation. Furthermore, TNFRSF1A is a major mediator of both basal and TNFα-induced NF-κB activity in breast cancer cells. We extended these findings to primary human breast cancers, in which we found that high TNFRSF1A transcript levels correlated with STAT3 activation. In addition, and consistent with a causal role, increased TNFRSF1A expression was associated with an NF-κB gene expression in signature in breast cancers. Thus, TNFRSF1A is a STAT3 target gene that regulates the NF-κB pathway. These findings reveal a novel functional crosstalk between STAT3 and NF-κB signaling in breast cancer. Furthermore, elevated TNFRSF1A levels may predict a subset of breast tumors that are sensitive to STAT3 transcriptional inhibitors, and may be a biomarker for response to inhibition of this pathway.
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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.