ArticleCell death and differentiation2023
USP51 facilitates colorectal cancer stemness and chemoresistance by forming a positive feed-forward loop with HIF1A.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
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- CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.Molecular cancer · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- SOCS1 depletion drives osteosarcoma stemness and chemoresistance by suppressing ACTN4 degradation.Acta pharmacologica Sinica · 2026Article
- Long non-coding RNAs in the crosstalk between diabetes and colorectal cancer: molecular mechanisms and endocrine pathways.Frontiers in molecular biosciences · 2026Review
- Long non-coding RNAs as molecular links and circulating biomarkers between type 2 diabetes and colorectal cancer: focus on shared signaling pathways, epigenetic regulation, and ubiquitination mechanisms.Frontiers in molecular biosciences · 2026Review
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- ZNF454-FSTL3 axis inhibits colorectal cancer progression by inhibiting HIF-1α-mediated glycolysis in hypoxia.Journal of gastrointestinal oncology · 2025Article
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- Multi-omic characterization of consensus molecular subtype 1 (CMS1) colorectal cancer with dampened immune response improves precision medicine.Molecular oncology · 2025Article
- Ubiquitin-specific proteases as key regulators in the malignant progression and therapy resistance of colorectal cancer: current insights and future perspectives.Discover oncology · 2025Review
- UHRF1-mediated HIF-1α stabilization promotes ovarian cancer through metabolic reprogramming and angiogenesis.Cell death & disease · 2025Article
- SENP1 drives glycolysis and cisplatin resistance in gastric cancer via desumoylating ENO1.Journal of experimental & clinical cancer research : CR · 2025Article
- Novel insights into lncRNAs as key regulators of post-translational modifications in cancer: mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- SENP1: A perspective from immune cells to disease (Review).Oncology reports · 2025Review
- Regulation of divergent epithelial-to-mesenchymal transition responses via the CDK4/6-USP51 pathway through ZEB1 protein stabilization.Scientific reports · 2025Article
- Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.The Journal of clinical investigation · 2025Article
- USP39 promote post-translational modifiers to stimulate the progress of cancer.Discover oncology · 2025Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the current study, we have shown that USP51 promotes colorectal cancer stemness and chemoresistance, and high expression of USP51 predicts survival disadvantage in colorectal cancer patients. Mechanically, USP51 directly binds to Elongin C (ELOC) and forms a larger functional complex with VHL E3 ligase (USP51/VHL/CUL2/ELOB/ELOC/RBX1) to regulate the ubiquitin-dependent proteasomal degradation of HIF1A. USP51 efficiently deubiquitinates HIF1A and activates hypoxia-induced gene transcription. Conversely, the activation of HIF1A under hypoxia transcriptionally upregulates the expression of USP51. Thus, USP51 and HIF1A form a positive feedback loop. Further, we found that the SUMOylation of ELOC at K32 inhibits its binding to USP51. SUMO-specific protease 1 (SENP1) mediates the deSUMOylation of ELOC, promoting the binding of USP51 to ELOC and facilitating the deubiquitination and stabilization of HIF1A by USP51. Importantly, USP51 plays a crucial role in promoting the HIF1A and SENP1-dependent proliferation, migration, stemness, and chemoresistance under hypoxia in colorectal cancer. Together, our data revealed that USP51 is an oncogene stabilizing the pro-survival protein HIF1A, offering a potential therapeutic target for colorectal cancer.
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