ArticleMolecular and cellular biology1997
Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 523 citations in OpenAlex.
- Neurological recovery and antioxidant effect of erythropoietin for spinal cord injury: A systematic review and meta-analysis.Frontiers in neurology · 2022Pooled it
- CYP8B1 inhibits hepatocellular carcinoma progression by repressing PAK4 transcription through inhibition of nuclear translocation of u-STAT1.Cell death & disease · 2025Article
- Evaluation of Apoptosis and Cytotoxicity Induction Using a Recombinant Newcastle Disease Virus Expressing Human IFN-γ in Human Prostate Cancer Cells In Vitro.Biomedicines · 2025Article
- STAT1 increases the sensitivity of lung adenocarcinoma to carbon ion irradiation via HO-1-mediated ferroptosis.Molecular and cellular biochemistry · 2025Article
- FoxO1 promotes high glucose-induced inflammation and cataract formation via JAK1/STAT1.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.Frontiers in oncology · 2025Review
- Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.Inflammation · 2024Article
- Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin.International journal of molecular sciences · 2024Review
- Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.Essays in biochemistry · 2023Review
- Engineer a double team of short-lived and glucose-sensing bacteria for cancer eradication.Cell reports. Medicine · 2023Article
- Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell- and CXCR3-dependent manner.JCI insight · 2023Article
- Interplay between Signaling Pathways and Tumor Microenvironment Components: A Paradoxical Role in Colorectal Cancer.International journal of molecular sciences · 2023Review
- Cold Storage Followed by Transplantation Induces Interferon-Gamma and STAT-1 in Kidney Grafts.International journal of molecular sciences · 2023Article
- Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy.Frontiers in immunology · 2023Review
- IFN-γ and TGF-β, Crucial Players in Immune Responses: A Tribute to Howard Young.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models.Life science alliance · 2022Article
- Primary cilia contribute to the aggressiveness of atypical teratoid/rhabdoid tumors.Cell death & disease · 2022Article
- Role of JAK-STAT and PPAR-Gamma Signalling Modulators in the Prevention of Autism and Neurological Dysfunctions.Molecular neurobiology · 2022Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here we show that gamma interferon (IFN-gamma) activated STAT1 and induced apoptosis in both A431 and HeLa cells, whereas epidermal growth factor (EGF) activated STAT proteins and induced apoptosis in A431 but not in HeLa cells. EGF receptor autophosphorylation and mitogen-activated protein kinase activation in response to EGF were similar in both cell lines. The breast cancer cell line MDA-MB-468 exhibited a similar response to A431 cells, i.e., STAT activation and apoptosis correlatively resulted from EGF or IFN-gamma treatment. In addition, in a mutant A431 cell line in which STAT activation was abolished, no apoptosis was induced by either EGF or IFN-gamma. We further demonstrated that both EGF and IFN-gamma induced caspase 1 (interleukin-1beta converting enzyme [ICE]) gene expression in a STAT-dependent manner. IFN-gamma was unable to induce ICE gene expression and apoptosis in either JAK1-deficient HeLa cells (E2A4) or STAT1-deficient cells (U3A). However, ICE gene expression and apoptosis were induced by IFN-gamma in U3A cells into which STAT1 had been reintroduced. Moreover, both EGF-induced apoptosis and IFN-gamma-induced apoptosis were effectively blocked by Z-Val-Ala-Asp-fluoromethylketone (ZVAD) in all the cells tested, and studies from ICE-deficient cells indicated that ICE gene expression was necessary for IFN-gamma-induced apoptosis. We conclude that activation of the STAT signaling pathway can induce apoptosis through the induction of ICE gene expression.
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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.