ArticleCell death & disease2024
The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- The Efficacy of Pembrolizumab Immunotherapy in the Treatment of Endometrial Cancer: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Camptothecin Nanowires Induce the cGAS-STING Pathway to Remold Tumor-Associated Macrophages for Antitumor Immunity.Pharmaceutics · 2026Article
- ATM immunohistochemistry as an effective screening method for POLE variants among endometrial carcinomas lacking mismatch repair deficiency and p53 abnormalities.The journal of pathology. Clinical research · 2026Article
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- Natural killer cells at the interface of tumor immune escape and immunotherapy resistance in endometrial cancer.Frontiers in immunology · 2026Review
- ctDNA guided management of POLE mutant GI malignancies promotes exceptional responses and prolonged survival to immunotherapy.Frontiers in immunology · 2026Article
- XPO1 R749Q Mutations Co-occur with POLE Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance.Cancer research · 2025Article
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values.Frontiers in immunology · 2025Review
- Lamins regulate cancer cell plasticity and chemosensitivity.Frontiers in oncology · 2025Article
- Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection.International journal of molecular sciences · 2024Review
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- The cGAS-STING pathway and female reproductive system diseases.Frontiers in immunology · 2024Review
- The prognostic implication of polymerase epsilon-mutated endometrial cancer.Tzu chi medical journalReview
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
Endometrial carcinoma (EC) is a prevalent gynecological tumor in women, and its treatment and prevention are significant global health concerns. The mutations in DNA polymerase ε (POLE) are recognized as key features of EC and may confer survival benefits in endometrial cancer patients undergoing anti-PD-1/PD-L1 therapy. However, the anti-tumor mechanism of POLE mutations remains largely elusive. This study demonstrates that the hot POLE P286R mutation impedes endometrial tumorigenesis by inducing DNA breakage and activating the cGAS-STING signaling pathway. The POLE mutations were found to inhibit the proliferation and stemness of primary human EC cells. Mechanistically, the POLE mutants enhance DNA damage and suppress its repair through the interaction with DNA repair proteins, leading to genomic instability and the upregulation of cytoplasmic DNA. Additionally, the POLE P286R mutant also increases cGAS level, promotes TBK1 phosphorylation, and stimulates inflammatory gene expression and anti-tumor immune response. Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective 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.