ArticleCell death and differentiation2023
USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer.
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 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Circulating proteins associated with histological subtypes of lung cancer from genetic and population-based perspectives.PLoS genetics · 2025Pooled it
- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Magnesium isoglycyrrhizinate alleviates alcohol-associated liver disease through targeting HSD11B1.eLife · 2026Article
- Pre-diagnostic metabolites in peripheral blood of Langerhans cell histiocytosis children with posterior pituitary involvement.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Spatial Multiomics Analyses Reveal That Diabetes Promotes Pancreatic Cancer Progression by Stimulating Cholesterol-Induced Neutrophil Extracellular Trap Formation.Cancer research · 2026Article
- Aneuploidy sensitizes cells to SREBP-pathway inhibition in squamous cell carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Accurate profiling of single-cell alternative transcript start sites by correcting RNA degradation.Nature communications · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- SREBP2 confers ferroptosis resistance by targeting GPX4 in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Pathological role of deubiquitinating enzymes in lung cancer: recent insights and advances.American journal of cancer research · 2026Review
- Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance.Frontiers in immunology · 2026Review
- USP28 Promotes Osimertinib Resistance in H1975 NSCLC Cells by Deubiquitinating and Stabilizing SIRT1.The Kaohsiung journal of medical sciences · 2026Article
- SREBP-2 promotes cancer progression through the mevalonate-Akt pathway in non-small cell lung cancer.Scientific reports · 2025Article
- USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer.Cell death & disease · 2025Article
- The deubiquitinase USP28 maintains the expression of PPARγ and its inactivation protects mice from diet-induced MASH and hepatocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting piRNA-137463 Inhibits Tumor Progression and Boosts Sensitivity to Immune Checkpoint Blockade via De Novo Cholesterol Biosynthesis in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- SREBP2 as a central player in cancer progression: potential for targeted therapeutics.Frontiers in pharmacology · 2025Review
- The role of ubiquitination and deubiquitination in cancer lipid metabolism.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SREBP2 is a master regulator of the mevalonate pathway (MVP), a biosynthetic process that drives the synthesis of dolichol, heme A, ubiquinone and cholesterol and also provides substrates for protein prenylation. Here, we identify SREBP2 as a novel substrate for USP28, a deubiquitinating enzyme that is frequently upregulated in squamous cancers. Our results show that silencing of USP28 reduces expression of MVP enzymes and lowers metabolic flux into this pathway. We also show that USP28 binds to mature SREBP2, leading to its deubiquitination and stabilisation. USP28 depletion rendered cancer cells highly sensitive to MVP inhibition by statins, which was rescued by the addition of geranyl-geranyl pyrophosphate. Analysis of human tissue microarrays revealed elevated expression of USP28, SREBP2 and MVP enzymes in lung squamous cell carcinoma (LSCC) compared to lung adenocarcinoma (LADC). Moreover, CRISPR/Cas-mediated deletion of SREBP2 selectively attenuated tumour growth in a KRas/p53/LKB1 mutant mouse model of lung cancer. Finally, we demonstrate that statins synergise with a dual USP28/25 inhibitor to reduce viability of SCC cells. Our findings suggest that combinatorial targeting of MVP and USP28 could be a therapeutic strategy for the treatment of squamous cell carcinomas.
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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.