ArticleGut2024
Targeting MYC effector functions in pancreatic cancer by inhibiting the ATPase RUVBL1/2.
Article in Gut, 2024. 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.
- Genome-scale perturbation signatures from primary human CD4bioRxiv : the preprint server for biology · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Targeting RuvBL1 disrupts mitochondrial metabolism and structure in hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2026Article
- Rapid Optimization Enabled by Single-Molecule Tracking: Discovery of a Potent RUVBL1/2 Inhibitor to Evaluate the Targeting of MYC-Driven Cancers.Journal of medicinal chemistry · 2026Article
- Mapping Genetic Regulation of Transcription to Identify Functional Variants and Genes Associated with Pancreatic Cancer Risk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Construction and validation of a prognostic model associated with chromatin remodeling in hepatocellular carcinoma.Translational cancer research · 2026Article
- Identification of Small Extracellular Vesicle (sEV)-Related Genes and the Establishment of Diagnostic Models for Esophageal Cancer.Current medicinal chemistry · 2026Article
- KLF5 enables dichotomous lineage programs in pancreatic cancer via the AAA+ ATPase coactivators RUVBL1 and RUVBL2.Nature communications · 2025Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- MYC: The Guardian of Its Own Chaos.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The Lyn/RUVBL1 Complex Promotes Colorectal Cancer Liver Metastasis by Regulating Arachidonic Acid Metabolism Through Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.Oncogene · 2024Article
- Molecular Signatures of CB-6644 Inhibition of the RUVBL1/2 Complex in Multiple Myeloma.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC).
designTo identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice.
resultsUnexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases RUVBL1 and RUVBL2 ranked first. Degradation of RUVBL1 by the auxin-degron system led to the arrest of cultured PDAC cells but not untransformed cells and to complete tumour regression in mice, which was preceded by immune cell infiltration. Mechanistically, RUVBL1 was required for MYC to establish oncogenic and immunoevasive gene expression identifying the RUVBL1/2 complex as a druggable vulnerability in MYC-driven cancer.
conclusionOne implication of our study is that PDAC cell dependencies are strongly influenced by the environment, so genetic screens should be performed in vitro and in vivo. Moreover, the auxin-degron system can be applied in a PDAC model, allowing target validation in living mice. Finally, by revealing the nuclear functions of the RUVBL1/2 complex, our study presents a pharmaceutical strategy to render pancreatic cancers potentially susceptible to immunotherapy.
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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.