ArticleOncotarget2016
Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
18 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Origin recognition complex subunit 1 functions as an oncogenic driver and therapeutic target in cancer.Discover oncology · 2025Review
- GANT61 surmounts drug resistance of ADR by upregulating lysosome activities and reducing BCL2 expression in HL-60/ADR cells.Cancer cell international · 2024Article
- Structure Characterization of Zinc Finger Motif 1 and 2 of GLI1 DNA Binding Region.International journal of molecular sciences · 2024Article
- Circular RNAs in Cell Cycle Regulation of Cancers.International journal of molecular sciences · 2024Review
- Oncogenic KRASG12D Reprograms Lipid Metabolism by Upregulating SLC25A1 to Drive Pancreatic Tumorigenesis.Cancer research · 2023Article
- Hedgehog signaling via its ligand DHH acts as cell fate determinant during skeletal muscle regeneration.Nature communications · 2023Article
- Modulation of Hedgehog Signaling for the Treatment of Basal Cell Carcinoma and the Development of Preclinical Models.Biomedicines · 2022Review
- Delivery of Targeted Co(III)-DNA Inhibitors of Gli Proteins to Disrupt Hedgehog Signaling.Bioconjugate chemistry · 2022Article
- Mediators of human ureteral smooth muscle contraction-a role for erythropoietin, tamsulosin and Gli effectors.Translational andrology and urology · 2021Article
- FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer.Cancers · 2021Review
- Structure-based virtual screening identifies an 8-hydroxyquinoline as a small molecule GLI1 inhibitor.Molecular therapy oncolytics · 2021Article
- GLI1: A Therapeutic Target for Cancer.Frontiers in oncology · 2021Review
- GLI1 Inhibitor SRI-38832 Attenuates Chemotherapeutic Resistance by Downregulating NBS1 Transcription in BRAFFrontiers in oncology · 2020Article
- Regulation of fibroblast-like synoviocyte transformation by transcription factors in arthritic diseases.Biochemical pharmacology · 2019Review
- The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis.Molecular cancer · 2019Review
- Pharmacological targeting of GLI1 inhibits proliferation, tumor emboli formation and in vivo tumor growth of inflammatory breast cancer cells.Cancer letters · 2017Article
- Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability.Genes · 2016Review
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
The GLI genes are transcription factors and in cancers are oncogenes, aberrantly and constitutively activated. GANT61, a specific GLI inhibitor, has induced extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter. Pretreatment of HT29 cells with α-amanitin reduced GANT61-induced γH2AX foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1 and DNA replication to be linked. By co-immunoprecipitation and confocal microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1 was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29 and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of caspase-3. Data demonstrate involvement of transcription and of DNA replication licensing factors by non-transcriptional and transcriptional mechanisms in the GLI-dependent mechanism of action of GANT61.
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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.