ArticleJournal of experimental & clinical cancer research : CR2019
SKP2 promotes breast cancer tumorigenesis and radiation tolerance through PDCD4 ubiquitination.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed.
- SKP2 Regulates Pulmonary Inflammatory Injury Triggered by Bacterial Infection Through p27-Mediated Degradation of FOXN3.MedComm · 2026Article
- E3 ligase RNF145 regulates airway smooth muscle cell proliferation via the PP2A-p70S6K signaling axis.The Journal of biological chemistry · 2026Article
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- Exosomal miR-373-3p Derived from Docetaxel-Resistant Lung Cancer Cells Targets PDCD4 to Promote Proliferation and Inhibit Apoptosis in Lung Cancer Cells.Biomedicines · 2026Article
- Article
- Curcumol Induces G1 Phase Arrest in SK-Hep-1 Cells by Targeting SKP2-Mediated p27 Degradation.Molecules (Basel, Switzerland) · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma.PloS one · 2026Article
- Mutant NPM1 modulates PDCD4 ubiquitination degradation and facilitates leukemogenesis.iScience · 2025Article
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- MARCH1, transcriptionally regulated by POU2F2, facilitates acute myeloid leukemia progression via inducing MYCT1 degradation.Oncogene · 2025Article
- m6A reader IGF2BP2-stabilized lncRNA LHX1-DT inhibits renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-590-5p.NPJ precision oncology · 2025Article
- MicroRNA-21 Promotes the Viability, Proliferation and Milk Fat Synthesis of Ovine Mammary Epithelial Cells by TargetingInternational journal of molecular sciences · 2025Article
- Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy.Nature communications · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- Targeting Molecular Pathways in Breast Cancer Using Plant-Derived Bioactive Compounds: A Comprehensive Review.Journal of experimental pharmacology · 2025Review
- An Updated Review of Molecular Mechanisms Implicated with the Anticancer Potential of Diosgenin and Its Nanoformulations.Drug design, development and therapy · 2025Review
- A Chemotherapy Response-Related Gene Signature and DNAJC8 as Key Mediators of Hepatocellular Carcinoma Progression and Drug Resistance.Journal of hepatocellular carcinoma · 2025Article
- Hypoxia-induced S-phase kinase-interacting protein 2 knockdown repressed the progression of melanoma through extracellular signal-regulated kinase 1/2 pathway.CytoJournal · 2025Article
- Energy restriction inhibits β-catenin ubiquitination to improve ischemic stroke injury via USP18/SKP2 axis.Metabolic brain disease · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundS-phase kinase-associated protein 2 (SKP2) is an oncogene and cell cycle regulator that specifically recognizes phosphorylated cell cycle regulator proteins and mediates their ubiquitination. Programmed cell death protein 4 (PDCD4) is a tumor suppressor gene that plays a role in cell apoptosis and DNA-damage response via interacting with eukaryotic initiation factor-4A (eIF4A) and P53. Previous research showed SKP2 may interact with PDCD4, however the relationship between SKP2 and PDCD4 is unclear.
methodsTo validate the interaction between SKP2 and PDCD4, mass spectrometric analysis and reciprocal co-immunoprecipitation (Co-IP) experiments were performed. SKP2 stably overexpressed or knockdown breast cancer cell lines were established and western blot was used to detect proteins changes before and after radiation. In vitro and in vivo experiments were performed to verify whether SKP2 inhibits cell apoptosis and promotes DNA-damage response via PDCD4 suppression. SMIP004 was used to test the effect of radiotherapy combined with SKP2 inhibitor.
resultsWe found that SKP2 remarkably promoted PDCD4 phosphorylation, ubiquitination and degradation. SKP2 promoted cell proliferation, inhibited cell apoptosis and enhanced the response to DNA-damage via PDCD4 suppression in breast cancer. SKP2 and PDCD4 showed negative correlation in human breast cancer tissues. Radiotherapy combine with SKP2 inhibitor SMIP004 showed significant inhibitory effects on breast cancer cells in vitro and in vivo.
conclusionsWe identify PDCD4 as an important ubiquitination substrate of SKP2. SKP2 promotes breast cancer tumorigenesis and radiation tolerance via PDCD4 degradation. Radiotherapy combine with SKP2-targeted adjuvant therapy may improve breast cancer patient survival in clinical medicine.
Indexed as
Identifiers
What OpenQuestion holds
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.