ArticleAging2021
Inhibiting USP8 overcomes hepatocellular carcinoma resistance via suppressing receptor tyrosine kinases.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Positive feedback regulation between USP8 and Hippo/YAP axis drives triple-negative breast cancer progression.Cell death & disease · 2026Article
- HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models.Histology and histopathology · 2026Article
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.NPJ precision oncology · 2025Article
- USP38: an important regulatory factor in tumor malignant progression.Frontiers in immunology · 2025Review
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway.World journal of clinical oncology · 2024Article
- Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.Current topics in medicinal chemistry · 2024Review
- USP3 inhibition is Active Against Chemo-resistant Hepatocellular Carcinoma Anchorage-independent GrowthCurrent molecular medicine · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- USP8 inhibitor-induced DNA damage activates cell cycle arrest, apoptosis, and autophagy in esophageal squamous cell carcinoma.Cell biology and toxicology · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Mitochondria, mitophagy, and the role of deubiquitinases as novel therapeutic targets in liver pathology.Journal of cellular biochemistry · 2022Review
- Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel's activity by suppressing the NF-kB signaling pathway.Frontiers in oncology · 2022Article
- Research Progress of DUB Enzyme in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- ARV-771 Acts as an Inducer of Cell Cycle Arrest and Apoptosis to Suppress Hepatocellular Carcinoma Progression.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-specific protease 8 (USP8) is a prototypic multidomain deubiquitinating enzyme with pleiotropic functions. We investigated the role of USP8 in hepatocellular carcinoma (HCC) by analyzing expression patterns of USP8 in HCC patients, and evaluating its functions and underlying signaling. Among 20 HCC patients investigated, we found that USP8 protein upregulation was a common phenomenon (17 out of 20) in HCC compared to normal liver tissue. Furthermore, the upregulation of USP8 was not associated with any clinicopathology. USP8 inhibition via genetic and pharmacological approaches resulted in growth inhibition and apoptosis induction in both sensitive and doxorubicin-resistant HCC cells. Of note, USP8 inhibition significantly enhanced doxorubicin or sorafenib's efficacy in HCC cells and mouse models. We further found that USP8 inhibition decreased levels of multiple receptor tyrosine kinases (RTKs) by ~90%, such as epidermal growth factor receptor (EGFR) and c-Met. Consistently, the downstream signaling regulated by RTKs was disrupted in HCC cells after USP8 inhibition, as shown by the decreased p-Akt, p-STAT3 and p-Raf. Our findings demonstrate that USP8 is a novel therapeutic target in HCC. Inhibiting USP8 has potential to overcome current drug resistance, particularly on HCC patients with high USP8 expression.
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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.