ArticleProceedings of the National Academy of Sciences of the United States of America2025
The E3 ligase HECTD4 regulates COX-2-dependent tumor progression and metastasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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
7 citing papers in PubMed.
- The deubiquitinating enzyme USP42 promotes lung adenocarcinoma progression through PTGS2.Journal of molecular histology · 2026Article
- HECTD4 in human umbilical cord mesenchymal stem cells-derived exosomes alleviates osteoclast differentiation in osteoporosis progression by suppressing RANK m6A modification via promoting METTL3 ubiquitination.Journal of molecular histology · 2026Article
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- Article
- The E3 ligase HECTD4 regulates COX-2-dependent tumor progression and metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Proteomic Profiling Reveals HECTD4-dependent Regulation of Protein Ubiquitination and Signaling Pathways in Prostate Cancer.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
E3 ubiquitin ligases mediating turnover of proteins engaged in cancer progression point to key regulatory nodes. To uncover modifiers of metastatic competency, we conducted an in vivo genome-wide CRISPR-inactivation screen using cultured breast circulating tumor cells, following intravascular seeding and lung colonization. We identified HECTD4, a previously uncharacterized gene encoding a conserved potential homologous to E6AP C-terminus domain-containing ubiquitin transferase, as a potent tumor and metastasis suppressor. We show that purified HECTD4 mediates ubiquitin conjugation in vitro, and proteomic studies combined with ubiquitin remnant profiling identify a major degradation target as the prostaglandin synthetic enzyme cyclooxygenase-2 (
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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.