ArticleJournal of biomedical science2022
A chemical probe inhibitor targeting STAT1 restricts cancer stem cell traits and angiogenesis in colorectal cancer.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- High expression of STAT3 and PD-L1 predicts poor prognosis for laryngeal squamous cell carcinoma.Scientific reports · 2026Article
- IGF2BP2 Drives Thyroid Cancer Dedifferentiation Through m6A-Dependent STAT1 mRNA Destabilization.International journal of biological sciences · 2026Article
- Beyond Rodents: Alternative Animal Models in Colorectal Cancer Research.International journal of molecular sciences · 2025Review
- A feedforward loop between STAT1 and YAP1 stimulates lipid biosynthesis, accelerates tumor growth, and promotes chemotherapy resistance in mutant KRAS colorectal cancer.Communications biology · 2025Article
- Activation of HTR2B Suppresses Osteosarcoma Progression through the STAT1-NLRP3 Inflammasome Pathway and Promotes OASL1+ Macrophage Production to Enhance Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Dissecting the immune evasion and therapeutic resistance mechanisms in EGFR/TP53 co-mutated non-small cell lung cancer: implications for targeted and immunotherapy strategies.Frontiers in immunology · 2025Article
- Targeting CREB-binding protein (CBP) abrogates colorectal cancer stemness through epigenetic regulation of C-MYC.Cancer gene therapy · 2024Article
- Fibroblast growth factor pathway promotes glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in prostate cancer.Journal of translational medicine · 2024Article
- Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- STAT3 drives the malignant progression of low-grade gliomas through modulating the expression of STAT1, FOXO1, and MYC.Frontiers in molecular biosciences · 2024Article
- Article
- Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches.Frontiers in immunology · 2024Article
- DDX18 drives tumor immune escape through transcription-activated STAT1 expression in pancreatic cancer.Oncogene · 2023Article
- Review
- STAT proteins in cancer: orchestration of metabolism.Nature reviews. Cancer · 2023Review
- Application of exosomal miRNA mediated macrophage polarization in colorectal cancer: Current progress and challenges.Oncology research · 2023Review
- Review
- Affinity probes based on small-molecule inhibitors for tumor imaging.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundColorectal cancer (CRC) is a worldwide cancer with rising annual incidence. New medications for patients with CRC are still needed. Recently, fluorescent chemical probes have been developed for cancer imaging and therapy. Signal transducer and activator of transcription 1 (STAT1) has complex functions in tumorigenesis and its role in CRC still needs further investigation.
methodsRNA sequencing datasets in the NCBI GEO repository were analyzed to investigate the expression of STAT1 in patients with CRC. Xenograft mouse models, tail vein injection mouse models, and azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were generated to study the roles of STAT1 in CRC. A ligand-based high-throughput virtual screening approach combined with SWEETLEAD chemical database analysis was used to discover new STAT1 inhibitors. A newly designed and synthesized fluorescently labeled 4',5,7-trihydroxyisoflavone (THIF) probe (BODIPY-THIF) elucidated the mechanistic actions of STAT1 and THIF in vitro and in vivo. Colonosphere formation assay and chick chorioallantoic membrane assay were used to evaluate stemness and angiogenesis, respectively.
resultsUpregulation of STAT1 was observed in patients with CRC and in mouse models of AOM/DSS-induced CRC and metastatic CRC. Knockout of STAT1 in CRC cells reduced tumor growth in vivo. We then combined a high-throughput virtual screening approach and analysis of the SWEETLEAD chemical database and found that THIF, a flavonoid abundant in soybeans, was a novel STAT1 inhibitor. THIF inhibited STAT1 phosphorylation and might bind to the STAT1 SH2 domain, leading to blockade of STAT1-STAT1 dimerization. The results of in vitro and in vivo binding studies of THIF and STAT1 were validated. The pharmacological treatment with BODIPY-THIF or ablation of STAT1 via a CRISPR/Cas9-based strategy abolished stemness and angiogenesis in CRC. Oral administration of BODIPY-THIF attenuated colitis symptoms and tumor growth in the mouse model of AOM/DSS-induced CRC.
conclusionsThis study demonstrates that STAT1 plays an oncogenic role in CRC. BODIPY-THIF is a new chemical probe inhibitor of STAT1 that reduces stemness and angiogenesis in CRC. BODIPY-THIF can be a potential tool for CRC therapy as well as cancer cell imaging.
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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.