ArticleOncogene2001
Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 312 papers.
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Who cites it
312 citing papers in PubMed.
- p-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial.International journal of oncology · 2018Trial
- First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy.Cancer discovery · 2012Trial
- Review
- The differential roles of Giardia duodenalis-secreted tenascins in inducing intestinal epithelial cell apoptosis and the attributed EGFR-STAT3 axis regulation.PLoS neglected tropical diseases · 2026Article
- 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
- STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts.Cell reports · 2026Article
- Targeting SRC to mediate solasonine's anti-cancer activity in hepatocellular carcinoma and its potential for multi-cancer therapy.Frontiers in oncology · 2026Article
- Novel p53 reactivators that are synergistic with olaparib for the treatment of gynecologic cancers with mutant p53.Translational oncology · 2025Article
- Pharmacological Inhibition of c-Jun N-Terminal Kinase Activity Exacerbates Liver Damage in Schistosoma mansoni Infected Mice.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Sublethal executioner caspase activation in hepatocytes promotes liver regeneration through the JAK/STAT3 pathway.PLoS biology · 2025Article
- Increased RhoA pathway activation downstream of αIIbβ3/SRC contributes to heterozygous Bernard Soulier syndrome.Haematologica · 2025Article
- CXCL6 Reshapes Lipid Metabolism and Induces Neutrophil Extracellular Trap Formation in Cholangiocarcinoma Progression and Immunotherapy Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oncometabolite D-2HG drives tumor metastasis and protumoral macrophage polarization by targeting FTO/mJournal of experimental & clinical cancer research : CR · 2025Article
- Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.The Journal of clinical investigation · 2025Article
- JAK-STAT Signaling in Autoimmunity and Cancer.ImmunoTargets and therapy · 2025Review
- Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation.Disease models & mechanisms · 2024Article
- Effects of heterologous kinase domains on growth factor receptor specificity.Cellular signalling · 2024Article
- Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.Cancers · 2024Review
- Synthesis and evaluation of [EJNMMI radiopharmacy and chemistry · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
252 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Constitutive activation of signal transducer and activator of transcription (STAT) proteins has been detected in a wide variety of human primary tumor specimens and tumor cell lines including blood malignancies, head and neck cancer, and breast cancer. We have previously demonstrated a high frequency of Stat3 DNA-binding activity that is constitutively-induced by an unknown mechanism in human breast cancer cell lines possessing elevated EGF receptor (EGF-R) and c-Src kinase activities. Using tyrosine kinase selective inhibitors, we show here that Src and JAK family tyrosine kinases cooperate to mediate constitutive Stat3 activation in the absence of EGF stimulation in model human breast cancer cell lines. Inhibition of Src or JAKs results in dose-dependent suppression of Stat3 DNA-binding activity, which is accompanied by growth inhibition and induction of programmed cell death. In addition, transfection of a dominant-negative form of Stat3 leads to growth inhibition involving apoptosis of breast cancer cells. These results indicate that the biological effects of the Src and JAK tyrosine kinase inhibitors are at least partially mediated by blocking Stat3 signaling. While EGF-R kinase activity is not required for constitutive Stat3 activation in breast cancer cells, EGF stimulation further increases STAT DNA-binding activity, consistent with an important role for EGF-R in STAT signaling and malignant progression. Analysis of primary breast tumor specimens from patients with advanced disease revealed that the majority exhibit elevated STAT DNA-binding activity compared to adjacent non-tumor tissues. Our findings, taken together, suggest that tyrosine kinases transduce signals through Stat3 protein that contribute to the growth and survival of human breast cancer cells in culture and potentially in vivo.
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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.