ArticleCancer research2012
Unphosphorylated STAT1 promotes sarcoma development through repressing expression of Fas and bad and conferring apoptotic resistance.
Article in Cancer research, 2012. 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.
- Signal Transduction and Transcription Activator 1 in Pan-Cancer: Prognostic and Immunological Value.Clinical and experimental medicine · 2026Article
- Apoptotic Cancer Cell-Primed Cancer-Associated Fibroblasts Suppress Immunosuppressive Macrophages via WISP-1-Integrin α5β3-STAT1 Signaling in Lung Cancer.International journal of biological sciences · 2026Article
- CYP8B1 inhibits hepatocellular carcinoma progression by repressing PAK4 transcription through inhibition of nuclear translocation of u-STAT1.Cell death & disease · 2025Article
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- Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes.Nature communications · 2025Article
- Elevated Type I Interferon Signaling Defines the Proliferative Advantage of ARF and p53 Mutant Tumor Cells.Molecular and cellular biology · 2025Article
- The emerging role of SARS-CoV-2 nonstructural protein 1 (nsp1) in epigenetic regulation of host gene expression.FEMS microbiology reviews · 2024Review
- Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy.Frontiers in immunology · 2023Review
- Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer.Cancer gene therapy · 2022Article
- A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer.Journal of biomedical science · 2022Article
- Modulating environmental signals to reveal mechanisms and vulnerabilities of cancer persisters.Science advances · 2022Article
- Seasonal variation in the morphokinetics ofFrontiers in reproductive health · 2022Article
- A pan-cancer analysis of the expression of STAT family genes in tumors and their relationship to the tumor microenvironment.Frontiers in oncology · 2022Article
- Role of the JAK/STAT Pathway in Cervical Cancer: Its Relationship with HPV E6/E7 Oncoproteins.Cells · 2020Review
- STAT1 as a potential prognosis marker for poor outcomes of early stage colorectal cancer with microsatellite instability.PloS one · 2020Article
- Predicting STAT1 as a prognostic marker in patients with solid cancer.Therapeutic advances in medical oncology · 2020Article
- Dichotomal functions of phosphorylated and unphosphorylated STAT1 in hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Review
- SATB1 siRNA-encapsulated immunoliposomes conjugated with CD44 antibodies target and eliminate gastric cancer-initiating cells.OncoTargets and therapy · 2018Article
- The tumor suppressor interferon regulatory factor 8 inhibits β-catenin signaling in breast cancers, but is frequently silenced by promoter methylation.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
STAT1 exists in phosphorylated (pSTAT1) and unphosphorylated (uSTAT1) forms each regulated by IFN-γ. Although STAT1 is a key mediator of the IFN-γ signaling pathway, an essential component of the host cancer immunosurveillance system, STAT1 is also overexpressed in certain human cancers where the functions of pSTAT1 and uSTAT1 are ill defined. Using a murine model of soft tissue sarcoma (STS), we show that disruption of the IFN effector molecule IRF8 decreases pSTAT1 and increases uSTAT1 in STS cells, thereby increasing their metastatic potential. We determined that the IRF8 gene promoter was hypermethylated frequently in human STS. An analysis of 123 human STS specimens revealed that high uSTAT1 levels in tumor cells was correlated with a reduction in disease-specific survival (DSS), whereas high pSTAT1 levels in tumor cells were correlated with an increase in DSS. In addition, uSTAT1 levels were negatively correlated with pSTAT1 levels in these STS specimens. Mechanistic investigations revealed that IRF8 suppressed STAT1 transcription by binding the STAT1 promoter. RNAi-mediated silencing of STAT1 in STS cells was sufficient to increase expression of the apoptotic mediators Fas and Bad and to elevate the sensitivity of STS cells to Fas-mediated apoptosis. Together, our findings show how the phosphorylation status of pSTAT1 determines its function as a tumor suppressor, with uSTAT1 acting as a tumor promoter that acts by elevating resistance to Fas-mediated apoptosis to promote immune escape.
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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.