ArticleCancer cell international2021
Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 9 citations in OpenAlex.
- CREB1-ROC1 axis drives bladder cancer progression under hypoxic conditions.Molecular and cellular biochemistry · 2026Article
- CMA-mediated USP9X degradation promotes SHH medulloblastoma progression by facilitating SUFU ubiquitination.Clinical and translational medicine · 2026Article
- BAP1-mediated stabilization of SUFU enhances E2F1 activity and promotes colorectal tumorigenesis.Cell communication and signaling : CCS · 2026Article
- Recent advances in bladder cancer stem cells (BCSCs): A descriptive review of emerging therapeutic targets.iScience · 2025Review
- Regulator of cullins-1 predicts a poor prognosis and regulates epithelial-mesenchymal transition process through GSK-3β/Wnt signaling in renal cell carcinoma.Translational andrology and urology · 2025Article
- FBXO32 ubiquitination of SUFU promotes progression and lenvatinib resistance in hepatocellular carcinoma via hedgehog signaling.Medical oncology (Northwood, London, England) · 2025Article
- Serum EZH2 is a novel biomarker for bladder cancer diagnosis and prognosis.Frontiers in oncology · 2024Article
- E3 ubiquitin ligases and deubiquitinases in bladder cancer tumorigenesis and implications for immunotherapies.Frontiers in immunology · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer.
methodsThis study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry.
resultsROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity.
conclusionThis study demonstrated that dysregulation of the ROC1-SUFU-GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.
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