ArticleOncogenesis2021
USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- USP29-regulated noncanonical stabilization of the hypoxia-inducible factor-α in aggressive prostate cancer.Molecular oncology · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- D-lactate and glycerol as potential biomarkers of sorafenib activity in hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- Stabilizing hepatic fatty acid oxidation: Editorial on "USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination".Clinical and molecular hepatology · 2025Article
- Deubiquitinase Ubiquitin-Specific Protease 29 Ameliorates Pathological Cardiac Hypertrophy through Inhibiting Transforming Growth Factor β-Activated Kinase 1.Journal of the American Heart Association · 2025Article
- Reprogramming of Glucose Metabolism by Nanocarriers to Improve Cancer Immunotherapy: Recent Advances and Applications.International journal of nanomedicine · 2025Review
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- USP29 alleviates the progression of MASLD by stabilizing ACSL5 through K48 deubiquitination.Clinical and molecular hepatology · 2025Article
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Long non‑coding RNA lung cancer‑associated transcript 1 regulates ferroptosis via microRNA‑34a‑5p‑mediated GTP cyclohydrolase 1 downregulation in lung cancer cells.International journal of oncology · 2024Article
- The regulation of hypoxia-related lncRNAs in hepatocellular carcinoma.Discover oncology · 2024Review
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL.Journal of experimental & clinical cancer research : CR · 2024Article
- USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer.Cancer cell international · 2024Article
- Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.Current topics in medicinal chemistry · 2024Review
- Oncogenic Alterations of Metabolism Associated with Resistance to Chemotherapy.Current molecular medicine · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Identification of USP29 as a key regulator of nucleotide biosynthesis in neuroblastoma through integrative analysis of multi-omics data.Cancer biology & therapy · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In hepatocellular carcinoma (HCC), aberrant expression of hypoxia-inducible factor 1 α (HIF1α) and increased aerobic glycolysis metabolism are drivers of resistance to therapy with the multi-kinase inhibitor Sorafenib. However, it has remained unknown how HIF1α is activated and how its activity and the subsequent induction of aerobic glycolysis promote Sorafenib resistance in HCC. Here, we report the ubiquitin-specific peptidase USP29 as a new regulator of HIF1α and of aerobic glycolysis during the development of Sorafenib resistance in HCC. In particular, we identified USP29 as a critical deubiquitylase (DUB) of HIF1α, which directly deubiquitylates and stabilizes HIF1α and, thus, promotes its transcriptional activity. Among the transcriptional targets of HIF1α is the gene encoding hexokinase 2 (HK2), a key enzyme of the glycolytic pathway. The absence of USP29, and thus of HIF1α transcriptional activity, reduces the levels of aerobic glycolysis and restores sensitivity to Sorafenib in Sorafenib-resistant HCC cells in vitro and in xenograft transplantation mouse models in vivo. Notably, the absence of USP29 and high HK2 expression levels correlate with the response of HCC patients to Sorafenib therapy. Together, the data demonstrate that, as a DUB of HIF1α, USP29 promotes Sorafenib resistance in HCC cells, in parts by upregulating glycolysis, thereby opening new avenues for therapeutically targeting Sorafenib-resistant HCC in patients.
Identifiers
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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.