ArticleJournal of cell science2015
SOX9 inhibits β-TrCP-mediated protein degradation to promote nuclear GLI1 expression and cancer stem cell properties.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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
37 citing papers in PubMed, 53 citations in OpenAlex.
- Replacing Antibiotics with Synergistic Probiotics-Microalgae Consortium in Mud Crab (Antibiotics (Basel, Switzerland) · 2026Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Sox9: A potential regulator of cancer stem cells in osteosarcoma.Open medicine (Warsaw, Poland) · 2024Review
- Review
- All-Trans Retinoic Acid Promotes a Tumor Suppressive OTUD6B-β-TrCP-SNAIL Axis in Esophageal Squamous Cell Carcinoma and Enhances Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- The crosstalk between long non-coding RNAs and the hedgehog signaling pathway in cancer.Medical oncology (Northwood, London, England) · 2022Review
- Review
- Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.International journal of molecular sciences · 2021Review
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
- Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer.Biomedicines · 2021Review
- The Role of Noncoding RNAs in the Regulation of Anoikis and Anchorage-Independent Growth in Cancer.International journal of molecular sciences · 2021Review
- Hedgehog Signaling and Truncated GLI1 in Cancer.Cells · 2020Review
- Connection of GLI1 variants to congenital heart disease susceptibility: A case-control study.Medicine · 2020Observational
- GLI3: a mediator of genetic diseases, development and cancer.Cell communication and signaling : CCS · 2020Review
- Oncogenic Mutations in Armadillo Repeats 5 and 6 of β-Catenin Reduce Binding to APC, Increasing Signaling and Transcription of Target Genes.Gastroenterology · 2020Article
- Cell Communication Network Factor 4 (CCN4/WISP1) Shifts Melanoma Cells from a Fragile Proliferative State to a Resilient Metastatic State.Cellular and molecular bioengineering · 2020Article
- Emerging role of F-box proteins in the regulation of epithelial-mesenchymal transition and stem cells in human cancers.Stem cell research & therapy · 2019Review
- WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial-mesenchymal transition.The Journal of biological chemistry · 2019Article
- SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer.Journal of oncology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The high mobility group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). In Kras transgenic mice, each of these factors are crucial for the development of PDA precursor lesions. SOX9 transcription is directly regulated by GLI1, but how SOX9 functions downstream of GLI1 is unclear. We observed positive feedback, such that SOX9-deficient PDA cells have severely repressed levels of endogenous GLI1, attributed to loss of GLI1 protein stability. SOX9 associated with the F-box domain of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase component, β-TrCP (also known as F-box/WD repeat-containing protein 1A), and suppressed its association with SKP1 and GLI1, a substrate of SCF-β-TrCP. SOX9 also tethered β-TrCP within the nucleus and promoted its degradation. SOX9 bound to β-TrCP through the SOX9 C-terminal PQA/S domain that mediates transcriptional activation. Suppression of β-TrCP in SOX9-deficient PDA cells restored GLI1 levels and promoted SOX9-dependent cancer stem cell properties. These studies identify SOX9-GLI1 positive feedback as a major determinant of GLI1 protein stability and implicate β-TrCP as a latent SOX9-bound tumor suppressor with the potential to degrade oncogenic proteins in tumor cells.
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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.