ArticleNature communications2023
The RNA-binding protein LRPPRC promotes resistance to CDK4/6 inhibition in lung cancer.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- BUB1 and CDK4/6 Dual Inhibition Increases Radiation Sensitivity in Glioblastoma, Lung Cancer, and Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Novel nuclear RNA export factor 1 adaptor drives tumor growth by increasing proliferation-stimulatory mRNA export.Signal transduction and targeted therapy · 2026Article
- Molecular glue that stabilizes the LRPPRC-MET-G4 interaction complex to drive MET downregulation.Nature communications · 2026Article
- C1orf35 contributes to high anabolic metabolism by simultaneously promoting aerobic glycolysis and oxidative phosphorylation in multiple myeloma cells.Cancer gene therapy · 2026Article
- Disulfide-Bridged Ru Complex-Mediated Photo-Disulfidptosis for Colorectal Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting LRPPRC lactylation disrupts metabolic-immune crosstalk and restores antitumor immunity in hepatocellular carcinoma.Translational cancer research · 2026Article
- Synergistic Anti-Tumor Activity of LRPPRC Inhibition and Dasatinib Through Dual Oxidative Phosphorylation Disruption.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Prognostic significance of genes associated with disulfidptosis in lung squamous cell carcinoma.Journal of cardiothoracic surgery · 2026Article
- LRPPRC-Driven Oxidative Phosphorylation Is Associated with Elesclomol-Induced Cuproptosis in Ovarian Cancer.International journal of molecular sciences · 2025Article
- LSD1 inhibition sensitizes anti-PD1 blockade immunotherapy by inhibiting the long-range attack of tumor-derived extracellular vesicles.Acta pharmaceutica Sinica. B · 2025Article
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- Lipin1-dependent transcriptional inactivation of SREBPs contributes to selinexor sensitivity in multiple myeloma.Acta pharmacologica Sinica · 2025Article
- Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis.Human cell · 2025Article
- An RNA transmethylation pathway governs kidney nephrogenic potential.Nature communications · 2025Article
- Targeting COPA to Enhance Erdafitinib Sensitivity in FGFR-Altered Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- LRPPRC confers enhanced oxidative phosphorylation metabolism in triple-negative breast cancer and represents a therapeutic target.Journal of translational medicine · 2025Article
- The deubiquitinase USP44 enhances cisplatin chemosensitivity through stabilizing STUB1 to promote LRPPRC degradation in neuroblastoma.Neuro-oncology · 2025Article
- RNA binding protein RBM22 suppresses non-small cell lung cancer tumorigenesis by stabilizing LATS1 mRNA.Journal of molecular histology · 2024Article
- Stable Dual miR-143 and miR-506 Upregulation Inhibits Proliferation and Cell Cycle Progression.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinase inhibitors against Cyclin Dependent Kinase 4 and 6 (CDK4/6i) are promising cancer therapeutic drugs. However, their effects are limited by primary or acquired resistance in virtually all tumor types. Here, we demonstrate that Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) controls CDK4/6i response in lung cancer by forming a feedback loop with CDK6. LRPPRC binds to CDK6-mRNA, increasing the stability and expression of CDK6. CDK6 and its downstream E2F Transcription Factor 1 (E2F1), bind to the LRPPRC promoter and elevate LRPPRC transcription. The activation of the LRPPRC-CDK6 loop facilitates cell cycle G1/S transition, oxidative phosphorylation, and cancer stem cell generation. Gossypol acetate (GAA), a gynecological medicine that has been repurposed as a degrader of LRPPRC, enhances the CDK4/6i sensitivity in vitro and in vivo. Our study reveals a mechanism responsible for CDK4/6i resistance and provides an enlightening approach to investigating the combinations of CDK4/6 and LRPPRC inhibitors in cancer therapy.
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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.