ArticleClinical and translational medicine2021
GRAMD4 inhibits tumour metastasis by recruiting the E3 ligase ITCH to target TAK1 for degradation in hepatocellular carcinoma.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- ZG16 represses tumor progression and M2 polarization of tumor-associated macrophages in hepatocellular carcinoma by promoting ubiquitination and degradation of SNX9 via binding to ITCH.Hepatology international · 2026Article
- A tale of dual role: HECT‑type E3 ubiquitin ligase mechanisms in liver diseases (Review).International journal of molecular medicine · 2026Review
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Single-cell analysis of the synovium and infrapatellar fat pad identifies key pathogenic genes and drug targets in osteoarthritis.International journal of clinical and experimental pathology · 2026Article
- Deciphering genetic susceptibility to clear cell renal cell carcinoma.Communications biology · 2025Article
- Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025Review
- Examining genotype-phenotype associations of GRAM domain proteins using GWAS, PheWAS and literature review in cattle, human, pig, mouse and chicken.Scientific reports · 2024Article
- PARVB deficiency alleviates cisplatin-induced tubular injury by inhibiting TAK1 signaling.Cellular and molecular life sciences : CMLS · 2024Article
- TAK1 deficiency promotes liver injury and tumorigenesis via ferroptosis and macrophage cGAS-STING signalling.JHEP reports : innovation in hepatology · 2023Article
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- NUF2 Drives Cholangiocarcinoma Progression and Migration via Inhibiting Autophagic Degradation of TFR1.International journal of biological sciences · 2023Article
- GRAMD4 inhibits tumour metastasis by recruiting the E3 ligase ITCH to target TAK1 for degradation in hepatocellular carcinoma.Clinical and translational medicine · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAberrant TAK1 (transforming growth factor β-activated kinase 1) activity is known to be involved in a variety of malignancies, but the regulatory mechanisms of TAK1 remain poorly understood. GRAMD4 (glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4) is a newly discovered p53-independent proapoptotic protein with an unclear role in HCC (hepatocellular carcinoma).
resultsIn this research, we found that GRAMD4 expression was lower in HCC samples, and its downregulation predicted worse prognosis for patients after surgical resection. Functionally, GRAMD4 inhibited HCC migration, invasion and metastasis. Mechanistically, GRAMD4 interacted with TAK1 to promote its protein degradation, thus, resulting in the inactivation of MAPK (Mitogen-activated protein kinase) and NF-κB pathways. Furthermore, GRAMD4 was proved to recruit ITCH (itchy E3 ubiquitin protein ligase) to promote the ubiquitination of TAK1. Moreover, high expression of TAK1 was correlated with low expression of GRAMD4 in HCC patients.
conclusionsGRAMD4 inhibits the migration and metastasis of HCC, mainly by recruiting ITCH to promote the degradation of TAK1, which leads to the inactivation of MAPK and NF-κB signalling pathways.
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