ArticlePNAS nexus2022
Genomic screening reveals ubiquitin-like modifier activating enzyme 1 as a potent and druggable target in c-MYC-high triple negative breast cancer models.
Article in PNAS nexus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 9 citations in OpenAlex.
- An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy.Cancer research · 2025Trial
- The ubiquitin-activating enzyme inhibitor TAK-243 activates store-operated CaBiochimica et biophysica acta. Molecular cell research · 2026Article
- Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Appraisal of CRISPR Technology as an Innovative Screening to Therapeutic Toolkit for Genetic Disorders.Molecular biotechnology · 2026Review
- Prognostic Impact of UBA1 Expression in Breast Cancer.Journal of Cancer · 2026Article
- Targeting SUMOylation promotes cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma.Nature communications · 2025Article
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- UBA1 inhibition sensitizes cancer cells to PARP inhibitors.Cell reports. Medicine · 2024Article
- Two-Dimensional Polyacrylamide Gel Electrophoresis Coupled with Nanoliquid Chromatography-Tandem Mass Spectrometry-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in the MCF7 Breast Cancer Cell Line Transfected for Jumping Translocation Breakpoint Protein Overexpression.International journal of molecular sciences · 2023Article
- A Comparison of Di- and Trinuclear Platinum Complexes Interacting with Glycosaminoglycans for Targeted Chemotherapy.ACS medicinal chemistry letters · 2023Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer (BC)-related deaths, despite accounting for only 10% to 15% of total BC cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the ubiquitin-like modifier activating enzyme 1 (UBA1). Targeting UBA1 with the first-in-class UBA1 inhibitor TAK-243 induced unresolvable endoplasmic reticulum (ER)-stress and activating transcription factor 4 (ATF4)-mediated upregulation of proapoptotic NOXA, leading to cell death. c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. Moreover, in an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden, indicating UBA1 is a potential new target in TNBC expressing high levels of c-MYC.
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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.