ArticleCancers2020
Hakin-1, a New Specific Small-Molecule Inhibitor for the E3 Ubiquitin-Ligase Hakai, Inhibits Carcinoma Growth and Progression.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- E3 ubiquitin-ligase Hakai regulates LRP4 stability and Wnt/β-catenin signalling in colorectal cancer cells.iScience · 2026Article
- Epithelial-Mesenchymal Transition States and Metabolic Reprogramming Related Signatures Predict Prognosis and Therapeutic Responses in HER2-Positive Breast Cancer.Journal of clinical laboratory analysis · 2025Article
- Dynamics of epithelial-mesenchymal plasticity driving cancer drug resistance.Cancer pathogenesis and therapy · 2025Review
- Beyond destruction: emerging roles of the E3 ubiquitin ligase Hakai.Cellular & molecular biology letters · 2025Review
- TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies.Cells · 2025Review
- Revisiting Treatment Strategies: Addressing Epithelial-to-Mesenchymal Transition-Induced Resistance in Hepatocellular Carcinoma.BME frontiers · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.Frontiers in oncology · 2025Review
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- Review
- Current insights on m6A RNA modification in acute leukemia: therapeutic targets and future prospects.Frontiers in oncology · 2024Review
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- Daurisoline Inhibiting Tumor Angiogenesis and Epithelial-Mesenchymal Transition in Bladder Cancer by Mediating HAKAI Protein Stability.Iranian journal of pharmaceutical research : IJPR · 2022Article
- Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease.Scientific reports · 2022Article
- Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery.Cellular & molecular biology letters · 2022Article
- New insights into molecules and pathways of cancer metabolism and therapeutic implications.Cancer communications (London, England) · 2021Review
- Regulation of Epithelial-Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer.Cancers · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The requirement of the E3 ubiquitin-ligase Hakai for the ubiquitination and subsequent degradation of E-cadherin has been associated with enhanced epithelial-to-mesenchymal transition (EMT), tumour progression and carcinoma metastasis. To date, most of the reported EMT-related inhibitors were not developed for anti-EMT purposes, but indirectly affect EMT. On the other hand, E3 ubiquitin-ligase enzymes have recently emerged as promising therapeutic targets, as their specific inhibition would prevent wider side effects. Given this background, a virtual screening was performed to identify novel specific inhibitors of Hakai, targeted against its phosphotyrosine-binding pocket, where phosphorylated-E-cadherin specifically binds. We selected a candidate inhibitor, Hakin-1, which showed an important effect on Hakai-induced ubiquitination. Hakin-1 also inhibited carcinoma growth and tumour progression both in vitro, in colorectal cancer cell lines, and in vivo, in a tumour xenograft mouse model, without apparent systemic toxicity in mice. Our results show for the first time that a small molecule putatively targeting the E3 ubiquitin-ligase Hakai inhibits Hakai-dependent ubiquitination of E-cadherin, having an impact on the EMT process. This represents an important step forward in a future development of an effective therapeutic drug to prevent or inhibit carcinoma tumour progression.
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What OpenQuestion holds
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.