ArticleMolecular cell2020
Hyperactive CDK2 Activity in Basal-like Breast Cancer Imposes a Genome Integrity Liability that Can Be Exploited by Targeting DNA Polymerase ε.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Design, synthesis, anticancer activity, and mechanistic investigation of 4,5,6,7-tetrahydrobenzo[Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Targeting DNA Polymerase Epsilon Induces Tumor Clearance and Activates an NF-κB-Mediated Inflammatory Response in Triple-Negative Breast Cancer.Cancer research · 2026Article
- Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Redox cycling nitroxide limits cellular iron availability and selectively inhibits iron-sulfur cluster metabolism.Cell death discovery · 2026Article
- Systematic Evaluation Defines the Limits of Ferroptosis in Cancer Therapy.bioRxiv : the preprint server for biology · 2026Article
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- NFS1 Plays a Critical Role in Regulating Ferroptosis Homeostasis.Biomolecules · 2025Review
- The genetic and biochemical basis of human leading strand synthesis.Nature communications · 2025Article
- The CIC::DUX4 oncoprotein maintains DNA integrity through direct regulation of the catalytic subunit of DNA polymerase epsilon (POLE).Oncogene · 2025Article
- Targeting DNA Polymerase Epsilon Leads to Tumor Clearance and Activation of an NF-κB-mediated inflammatory response in Triple Negative Breast Cancer.bioRxiv : the preprint server for biology · 2025Article
- Metabolic profiling of adult and pediatric gliomas reveals enriched glucose availability in pediatric gliomas and increased fatty acid oxidation in adult gliomas.Acta neuropathologica communications · 2025Article
- Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration.Open life sciences · 2025Article
- NFS1 inhibits ferroptosis in gastric cancer by regulating the STAT3 pathway.Journal of bioenergetics and biomembranes · 2024Article
- Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.International journal of molecular sciences · 2024Article
- Iron, Copper, and Selenium: Cancer's Thing for Redox Bling.Cold Spring Harbor perspectives in medicine · 2024Review
- Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.Molecules (Basel, Switzerland) · 2024Article
- NFS1 as a Candidate Prognostic Biomarker for Gastric Cancer Correlated with Immune Infiltrates.International journal of general medicine · 2024Article
- Immortalization-upregulated protein promotes pancreatic cancer progression by regulating NPM1/FHL1-mediated cell-cycle-checkpoint protein activity.Cell biology and toxicology · 2023Article
- CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination.NAR cancer · 2023Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Knowledge of fundamental differences between breast cancer subtypes has driven therapeutic advances; however, basal-like breast cancer (BLBC) remains clinically intractable. Because BLBC exhibits alterations in DNA repair enzymes and cell-cycle checkpoints, elucidation of factors enabling the genomic instability present in this subtype has the potential to reveal novel anti-cancer strategies. Here, we demonstrate that BLBC is especially sensitive to suppression of iron-sulfur cluster (ISC) biosynthesis and identify DNA polymerase epsilon (POLE) as an ISC-containing protein that underlies this phenotype. In BLBC cells, POLE suppression leads to replication fork stalling, DNA damage, and a senescence-like state or cell death. In contrast, luminal breast cancer and non-transformed mammary cells maintain viability upon POLE suppression but become dependent upon an ATR/CHK1/CDC25A/CDK2 DNA damage response axis. We find that CDK1/2 targets exhibit hyperphosphorylation selectively in BLBC tumors, indicating that CDK2 hyperactivity is a genome integrity vulnerability exploitable by targeting POLE.
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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.