ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Inhibition of CDK1 Overcomes Oxaliplatin Resistance by Regulating ACSL4-mediated Ferroptosis in Colorectal Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 140 citations in OpenAlex.
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- The Emerging Role of Ferroptosis in Pediatric Cancer Biology and Therapy.International journal of molecular sciences · 2026Review
- NRF2-CDH6-CEBPD axis suppresses ferroptosis and drives cisplatin resistance in non-small cell lung cancer.Journal of cell communication and signaling · 2026Article
- PUM2 inhibits ferroptosis and enhances oxaliplatin resistance in COAD via the NEDD4L/NRF2 axis.Translational oncology · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- The KAT8-CDK1 K33 acetylation axis drives doxorubicin resistance by suppressing ferroptosis and apoptosis in breast cancer.Cell death & disease · 2026Article
- Fatty Acid Metabolism and Hypoxia in the Tumor Microenvironment: Metabolic Adaptation and Clinical Potential in Colorectal Cancer.Biomedicines · 2026Review
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Review
- H4K8 lactylation-mediated ferroptosis defense drives EGFR-TKI resistance in lung adenocarcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Domain associated with zinc fingers-containing NF90-NF45 complex inhibits mFEBS open bio · 2026Article
- DCBLD1 as a novel prognostic biomarker and therapeutic target in breast cancer: clinical validation and mechanistic insights.Annals of medicine and surgery (2012) · 2026Article
- Combining ferroptosis inducers with gemcitabine to enhance treatment efficacy in pancreatic cancer.Cancer & metabolism · 2026Article
- TMEM184A promotes progression and drug resistance in colorectal cancer: a bioinformatics and clinical study.Scientific reports · 2026Article
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- Repression of FOSL1 augments ferroptosis to overcome oxaliplatin resistance in colorectal cancer by acting on SRSF2.Molecular biology reports · 2026Article
- Nicotine suppresses ferroptosis in colon cancer cells via HMOX1/NF-κB pathway to reduce oxaliplatin sensitivity.Apoptosis : an international journal on programmed cell death · 2026Article
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- <p>CDK1 depletion suppresses glioma malignancy through cell cycle pathway regulation: Mechanistic insights from functional and molecular profiling</p>.Oncology reports · 2026Article
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin-dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin-resistant cells and tissues due to the loss of N6-methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient-derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl-CoA synthetase long-chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron-dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin-resistant CRC.
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