ArticleOncotarget2012
Regulation of DNA damage following termination of Hedgehog (HH) survival signaling at the level of the GLI genes in human colon cancer.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 44 citations in OpenAlex.
- BAP1-mediated stabilization of SUFU enhances E2F1 activity and promotes colorectal tumorigenesis.Cell communication and signaling : CCS · 2026Article
- Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma.Molecular cancer therapeutics · 2023Article
- Targeting hedgehog-driven mechanisms of drug-resistant cancers.Frontiers in molecular biosciences · 2023Review
- Mir-326 potentiates radiosensitivity of cervical squamous cell carcinoma through downregulating SMO expression in the Hedgehog signaling pathway.Genes & genomics · 2022Article
- The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer.Oncology reports · 2020Article
- GLI1 Inhibitor SRI-38832 Attenuates Chemotherapeutic Resistance by Downregulating NBS1 Transcription in BRAFFrontiers in oncology · 2020Article
- Article
- Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture.International journal of molecular sciences · 2018Article
- Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy.OncoTargets and therapy · 2017Review
- The hedgehog inhibitor GANT61 sensitizes prostate cancer cells to ionizing radiation both in vitro and in vivo.Oncotarget · 2016Article
- Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both transcription and DNA licensing.Oncotarget · 2016Article
- In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors.Oncotarget · 2016Article
- Review
- Novel agents for advanced pancreatic cancer.Oncotarget · 2015Review
- Review
- Regulation of Hedgehog signaling by ubiquitination.Frontiers in biology · 2015Article
- Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis.Oncotarget · 2015Article
- Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy.Cancer biology & therapy · 2015Review
- Dysregulation of hedgehog signaling pathway related components in the evolution of colonic carcinogenesis.International journal of clinical and experimental medicine · 2015Article
- GLI inhibitor GANT-61 diminishes embryonal and alveolar rhabdomyosarcoma growth by inhibiting Shh/AKT-mTOR axis.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcriptional regulation of the Hedgehog (HH) signaling response is mediated by GLI genes (GLI1, GLI2) downstream of SMO, that are also activated by oncogenic signaling pathways. We have demonstrated the importance of targeting GLI downstream of SMO in the induction of cell death in human colon carcinoma cells. In HT29 cells inhibition of GLI1/GLI2 by the small molecule inhibitor GANT61 induced DNA double strand breaks (DSBs) and activation of ATM, MDC1 and NBS1; γH2AX and MDC1, NBS1 and MDC1 co-localized in nuclear foci. Early activation of ATM was decreased by 24 hr, when p-NBS1(Ser343), activated by ATM, was significantly reduced in cell extracts. Bound γH2AX was detected in isolated chromatin fractions or nuclei during DNA damage but not during DNA repair. MDC1 was tightly bound to chromatin at 32 hr as cells accumulated in early S-phase prior to becoming subG1, and during DNA repair. Limited binding of NBS1 was detected at all times during DNA damage but was strongly bound during DNA repair. Transient overexpression of NBS1 protected HT29 cells from GANT61-induced cell death, while knockdown of H2AX by H2AXshRNA delayed DNA damage signaling. Data demonstrate following GLI1/GLI2 inhibition: 1) induction of DNA damage in cells that are also resistant to SMO inhibitors, 2) dynamic interactions between γH2AX, MDC1 and NBS1 in single cell nuclei and in isolated chromatin fractions, 3) expression and chromatin binding properties of key mediator proteins that mark DNA damage or DNA repair, and 4) the importance of NBS1 in the DNA damage response mechanism.
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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.