ArticleJournal of experimental & clinical cancer research : CR2021
Targeting MUS81 promotes the anticancer effect of WEE1 inhibitor and immune checkpoint blocking combination therapy via activating cGAS/STING signaling in gastric cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- Replication Stress in Cancer: Mechanistic Insights and Therapeutic Opportunities for Radiosensitization.Current issues in molecular biology · 2026Review
- Negative regulators antagonizing antitumor innate immune pathways in lung cancer immune evasion.Frontiers in immunology · 2026Review
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma.Scientific reports · 2025Article
- Tumor-derived PRMT1 suppresses macrophage antitumor activity by inhibiting cGAS/STING signaling in gastric cancer cells.Cell death & disease · 2025Article
- TRIM6 ablation reverses ICB resistance in MSS gastric cancer by unleashing cGAS-STING-dependent antitumor immunity.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting WEE1 Kinase for Breast Cancer Therapeutics: An Update.International journal of molecular sciences · 2025Review
- STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- To cleave or not and how? The DNA exonucleases and endonucleases in immunity.Genes & diseases · 2025Review
- cGAS/STING pathway and gastrointestinal cancer: Mechanisms and diagnostic and therapeutic targets (Review).Oncology reports · 2025Review
- The balance of STING signaling orchestrates immunity in cancer.Nature immunology · 2024Review
- Adjuvant COX inhibition augments STING signaling and cytolytic T cell infiltration in irradiated 4T1 tumors.JCI insight · 2024Article
- IFNλ1 is a STING-dependent mediator of DNA damage and induces immune activation in lung cancer.Frontiers in immunology · 2024Article
- Article
- Metformin promotes cGAS/STING signaling pathway activation by blocking AKT phosphorylation in gastric cancer.Heliyon · 2023Article
- Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases.Archives of pharmacal research · 2023Review
- Hedgehog signaling-related genomics signature for the accurate progress and prognosis prediction in gastric cancer.Functional & integrative genomics · 2023Article
- Suppression of cGAS- and RIG-I-mediated innate immune signaling by Epstein-Barr virus deubiquitinase BPLF1.PLoS pathogens · 2023Article
- Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIdentification of genomic biomarkers to predict the anticancer effects of indicated drugs is considered a promising strategy for the development of precision medicine. DNA endonuclease MUS81 plays a pivotal role in various biological processes during malignant diseases, mainly in DNA damage repair and replication fork stability. Our previous study reported that MUS81 was highly expressed and linked to tumor metastasis in gastric cancer; however, its therapeutic value has not been fully elucidated.
methodsBioinformatics analysis was used to define MUS81-related differential genes, which were further validated in clinical tissue samples. Gain or loss of function MUS81 cell models were constructed to elucidate the effect and mechanism of MUS81 on WEE1 expression. Moreover, the antitumor effect of targeting MUS81 combined with WEE1 inhibitors was verified using in vivo and in vitro assays. Thereafter, the cGAS/STING pathway was evaluated, and the therapeutic value of MUS81 for immunotherapy of gastric cancer was determined.
resultsIn this study, MUS81 negatively correlated with the expression of cell cycle checkpoint kinase WEE1. Furthermore, we identified that MUS81 regulated the ubiquitination of WEE1 via E-3 ligase β-TRCP in an enzymatic manner. In addition, MUS81 inhibition could sensitize the anticancer effect of the WEE1 inhibitor MK1775 in gastric cancer in vitro and in vivo. Interestingly, when MUS81 was targeted, it increased the accumulation of cytosolic DNA induced by MK1775 treatment and activated the DNA sensor STING-mediated innate immunity in the gastric cancer cells. Thus, the WEE1 inhibitor MK1775 specifically enhanced the anticancer effect of immune checkpoint blockade therapy in MUS81 deficient gastric cancer cells.
conclusionsOur data provide rational evidence that targeting MUS81 could elevate the expression of WEE1 by regulating its ubiquitination and could activate the innate immune response, thereby enhancing the anticancer efficacy of WEE1 inhibitor and immune checkpoint blockade combination therapy in gastric cancer cells.
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