ArticleInternational journal of biological sciences2023
SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.
Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Emerging regulatory model of Ubiquitin-Specific Proteases 14 in cancer: from canonical oncogenesis to TME modulation, therapeutic resistance, and non-canonical activities.Journal of translational medicine · 2026Review
- USP14 promotes epithelial-mesenchymal transition and functions as a multifaceted biomarker in lung adenocarcinoma.Discover oncology · 2026Article
- CircKIAA1617 promotes stemness via USP14/PGRMC1-mediated autophagy and lipid metabolism reprogramming in ER-positive breast cancer.Molecular cancer · 2026Article
- Clinical Significance of SDC2 in Gastric Cancer: Insights From a Multi-Center Cohort Study.Cancer informatics · 2026Article
- Stool-based SDC2/SFRP2/TFPI2 methylation assay for colorectal neoplasia screening: a multicenter, case-control study.Frontiers in oncology · 2026Article
- Article
- XGB-BIF: An XGBoost-Driven Biomarker Identification Framework for Detecting Cancer Using Human Genomic Data.International journal of molecular sciences · 2025Article
- USP14 inhibits mitophagy and promotes tumorigenesis and chemosensitivity through deubiquitinating BAG4 in microsatellite instability-high colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.Biological research · 2024Article
- EZH2 Inhibition Enhances PD-L1 Protein Stability Through USP22-Mediated Deubiquitination in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.International journal of biological sciences · 2024Article
- Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer.Current medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer (GC) is a common malignancy and remains the fourth-leading cause of cancer-related deaths worldwide. Oncogenic potential of SDC2 has been implicated in multiple types of cancers, yet its role and underlying molecular mechanisms in GC remain unknown. Here, we found that SDC2 was highly expressed in GC and its upregulation correlated with poor prognosis in GC patients. Depletion of SDC2 significantly suppressed the growth and invasive capability of GC cells, while overexpressing SDC2 exerts opposite effects. Combined bioinformatics and experimental analyses substantiated that overexpression of SDC2 activated the AKT signaling pathway in GC, mechanistically through the interaction between SDC2 and PDK1-PH domain, thereby facilitating PDK1 membrane translocation to promote AKT activation. Moreover, SDC2 could also function as a co-receptor for FGF2 and was profoundly involved in the FGF2-AKT signaling axis in GC. Lastly, we revealed a mechanism on the USP14-mediated stabilization of SDC2 that is likely to contribute to SDC2 upregulation in GC tissues. Furthermore, we showed that IU1, a potent USP14 inhibitor, decreased the abundance of SDC2 in GC cells. Our findings indicate that SDC2 functions as a novel GC oncogene and has potential utility as a diagnostic marker and therapeutic target for GC.
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