ArticleCellular & molecular immunology2020
The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway.
Article in Cellular & molecular immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 69 citations in OpenAlex.
- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- Cavin gene family and caveolae-related disorders: pathogenetic roles and possible mechanisms.Cell communication and signaling : CCS · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Up-regulation of Ifi27l2a expression in bone marrow monocytes contributes to glucocorticoid-induced bone loss.Communications biology · 2025Article
- Anthracycline-induced cardiomyopathy in childhood cancer survivors is associated with gene signatures of mitochondrial dysfunction-a COG ALTE03N1 report.Cardio-oncology (London, England) · 2025Article
- CSF2RA promotes gastric cancer progression through activation of the JAK2/STAT3 signaling pathway.Journal of molecular histology · 2025Article
- Interferon-α and thymosin-α1 plus tislelizumab enhance CD8iScience · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- The KDM5A/HOXA5 axis regulates osteosarcoma progression via activating the Wnt/β-catenin pathway.European journal of medical research · 2025Article
- Downregulation of PD-L1 expression by Wnt pathway inhibition to enhance PD-1 blockade efficacy in hepatocellular carcinoma.Biology direct · 2025Article
- Identification of IFI27 involvement in the progression of neuroblastoma through bioinformatics analysis and experimental assays.Journal of molecular histology · 2025Article
- Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Decoding the molecular landscape: HER2 and PD-L1 in advanced gastric cancer.Frontiers in immunology · 2025Article
- Study on the molecular mechanism of matrine in improving rheumatoid arthritis by targeting the NAV2-Wnt3a/β-catenin axis to coordinately regulate the inflammatory-osteolytic loop.Frontiers in immunology · 2025Article
- SLC1A4 Promotes Malignant Transformation of Hepatocellular Carcinoma by Activating the AKT Signaling.Analytical cellular pathology (Amsterdam) · 2025Article
- IFI27 inhibits HIV-1 replication by degrading Gag protein through the ubiquitin-proteasome pathway.Journal of virology · 2024Article
- KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- Pan-cancer prognostic model and immune microenvironment analysis of natural killer cell-related genes.Translational cancer research · 2024Article
- ISG12a promotes immunotherapy of HBV-associated hepatocellular carcinoma through blocking TRIM21/AKT/β-catenin/PD-L1 axis.iScience · 2024Article
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Authors and funding
27 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to harness innate immunity is a promising solution for improving cancer immunotherapy. Interferon (IFN) induces expression of IFN-stimulated genes (ISGs) by activating the JAK-STAT signaling pathway to promote innate immunity and inhibit malignant tumor growth, but the functions and mechanisms of most ISGs in cancer regulation are unknown. As an innate immune effector, ISG12a promotes the innate immune response to viral infection. In this study, ISG12a was found to be expressed at low levels in gastrointestinal cancer, represented by hepatocellular cancer (HCC) and gastric cancer (GC), and it identified as a tumor suppressor that affects clinical prognosis. ISG12a silencing accelerated the malignant transformation and epithelial-mesenchymal transition of cancer cells. Mechanistically, ISG12a promoted β-catenin proteasomal degradation by inhibiting the degradation of ubiquitinated Axin, thereby suppressing the canonical Wnt/β-catenin signaling pathway. Notably, β-catenin was identified as a transcription factor for PD-L1. Inhibition of Wnt/β-catenin signaling by ISG12a suppressed expression of the immune checkpoint PD-L1, rendering cancer cells sensitive to NK cell-mediated killing. This study reveals a mechanism underlying the anticancer effects of IFN. Some ISGs, as represented by ISG12a, may be useful in cancer therapy and prevention. The identified interrelations among innate immunity, Wnt/β-catenin signaling, and cancer immunity may provide new insight into strategies that will improve the efficiency of immunotherapy.
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