ArticleMolecular cancer2017
Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer.
Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- SKP2 Regulates Pulmonary Inflammatory Injury Triggered by Bacterial Infection Through p27-Mediated Degradation of FOXN3.MedComm · 2026Article
- Tumor-Intrinsic PD-L1 Promotes Breast Cancer Proliferation Through Livin and Galectin-1-Mediated Regulation of SKP2 Expression.International journal of molecular sciences · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- E3 ubiquitin ligase SKP2 limits autophagosome formation duringFrontiers in cellular and infection microbiology · 2026Article
- Targeting Skp2 by Tanshinone IIA overcomes chemoresistance in colorectal cancer.Cell biology and toxicology · 2025Article
- Silencing of RNFT2 suppresses cell proliferation and migration through mTORC1 signaling pathway in gastric cancer.Amino acids · 2025Article
- Training and experimental validation a novel anoikis- and epithelial‒mesenchymal transition-related signature for evaluating prognosis and predicting immunotherapy efficacy in gastric cancer.Journal of Cancer · 2025Article
- Potential biomarkers in early detection of gastric cancer.Frontiers in pharmacology · 2025Review
- Targeting RCC1 to block the human soft-tissue sarcoma by disrupting nucleo-cytoplasmic trafficking of Skp2.Cell death & disease · 2024Article
- Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.Molecular therapy. Nucleic acids · 2024Article
- Therapeutic role of mTOR inhibitors in control of SARS-CoV-2 viral replication.Molecular biology reports · 2023Review
- SCF-SKP2 E3 ubiquitin ligase links mTORC1/ER stress/ISR with YAP activation in murine renal cystogenesis.The Journal of clinical investigation · 2022Article
- Review
- ABT-751 Induces Multiple Anticancer Effects in Urinary Bladder Urothelial Carcinoma-Derived Cells: Highlighting the Induction of Cytostasis through the Inhibition ofInternational journal of molecular sciences · 2021Article
- High S phase kinase-associated protein 2 expression is a potential prognostic biomarker for glioma.Oncology letters · 2020Article
- Clinicopathological features of pseudomyogenic hemangioendothelioma and precision therapy based on whole exome sequencing.Cancer communications (London, England) · 2020Article
- Systematically understanding the immunity leading to CRPC progression.PLoS computational biology · 2019Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- MiR-339 depresses cell proliferation via directly targeting S-phase kinase-associated protein 2 mRNA in lung cancer.Thoracic cancer · 2018Article
- S-phase kinase-associated protein 2 promotes cell growth and motility in osteosarcoma cells.Cell cycle (Georgetown, Tex.) · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth mTOR and Skp2 play critical roles in gastric cancer (GC) tumorigenesis. However, potential mechanisms for the association between these two proteins remains unidentified.
methodsThe regulatory role for mTORC1 in Skp2 stability was tested using ubiquitination assay. The functions of p-Skp2 (phosphorylation of Skp2) were studied in vitro and in vivo. Expression of p-Skp2 and p-mTOR (phosphorylation of mTOR) were shown in GC lines and in 169 human primary GC tissues.
resultsmTORC1 can directly interact with Skp2 and phosphorylated Skp2 at Ser64, which sequentially protect Skp2 from ubiquitination and degradation. Furthermore, the phospho-deficient p-Skp2 (S64) mutant significantly suppresses GC cell proliferation and tumorigenesis. The expression of p-Skp2 was associated with p-mTOR in GC cell lines and tissues. Interestingly, the combination of p-Skp2 and p-mTOR was a better predictor of survival than either factor alone.
conclusionThe mTORC1 function to regulate Skp2 by Ser64 phosphorylation may represent an oncogenic event in GC tumorigenesis. Moreover, our study also indicates that Skp2 Ser64 expression is a potential indicator in the treatment of GC patients using mTORC1 inhibitor.
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