ArticleJournal of gastroenterology2013
Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44⁺ gastric cancer cells via attenuating Wnt signaling.
Article in Journal of gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Recombinant adenoviruses application for cancer vaccines: from genetic design to clinical translation.Frontiers in oncology · 2026Review
- DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization.Applied biochemistry and biotechnology · 2025Article
- Review
- Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution.Engineering microbiology · 2024Review
- Review
- Calreticulin enhances gastric cancer metastasis by dimethylating H3K9 in the E-cadherin promoter region mediating by G9a.Oncogenesis · 2022Article
- Oncolytic virus: A catalyst for the treatment of gastric cancer.Frontiers in oncology · 2022Review
- Molecular subclassification of gastrointestinal cancers based on cancer stem cell traits.Experimental hematology & oncology · 2021Review
- The transcription factor RUNX2 fuels YAP1 signaling and gastric cancer tumorigenesis.Cancer science · 2021Article
- SHARPIN stabilizes β-catenin through a linear ubiquitination-independent manner to support gastric tumorigenesis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- Expression and Role of Dickkopf-1 (Dkk1) in Tumors: From the Cells to the Patients.Cancer management and research · 2021Review
- Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer.Frontiers in oncology · 2021Review
- Oncolytic Adenovirus: Prospects for Cancer Immunotherapy.Frontiers in microbiology · 2021Review
- FOXC1 Negatively Regulates DKK1 Expression to Promote Gastric Cancer Cell Proliferation Through Activation of Wnt Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Targeting Wnt Signaling for the Treatment of Gastric Cancer.International journal of molecular sciences · 2020Review
- NETO2 promotes invasion and metastasis of gastric cancer cells via activation of PI3K/Akt/NF-κB/Snail axis and predicts outcome of the patients.Cell death & disease · 2019Article
- Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway.Oncogene · 2018Article
- Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling.Cancer research · 2018Article
- Prognostic value of Dickkopf-1 and ß-catenin expression in advanced gastric cancer.BMC cancer · 2018Article
- Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastric cancer stem cells (CSCs), which require activation of Wnt signaling to maintain their self-renewal and tumorigenicity, are proposed to be critical targets for effective therapy of gastric carcinomas. Gene therapies that are delivered by adenovirus of serotype 5 (Ad5) or chimeric 5/35(Ad5/35) adenovirus have shown promise for treating various cancers. Here we aimed to develop a gene therapy strategy that targeted gastric CSCs (CD44⁺ cells).
methodsCD44⁺ cells were isolated by fluorescence activated cell sorting from both primary gastric cancer cells and cell lines. Expression of adenovirus receptors was examined in CD44⁺ and CD44⁻ cells. A potent Wnt antagonist Dickkopf-1 (DKK1) was delivered into CD44⁺ cells using Ad5/35 (Ad5/35-DKK1). The therapeutic outcomes were evaluated.
resultsExpression of Coxsakievirus adenovirus receptor for Ad5 was significantly reduced, while abundance of CD46, the receptor for Ad5/35, was slightly higher in CD44⁺ cells. Accordingly, CD44⁺ cells were sensitive to Ad5/35 infection, but not to Ad5. Ad5/35-DKK1 introduced DKK1 into CD44⁺ cells and deactivated endogenous Wnt/β-catenin signaling efficiently. Overexpression of DKK1 inhibited survival, anchorage-independent colony formation, and invasion of CD44⁺ cells, which were restored by a GSK-3 specific inhibitor BIO-acetoxime. More importantly, introduction of DKK1 abrogated the tumorigenicity of CD44⁺ cells in vivo. However, Ad5/35-DKK1 only showed minimal cytotoxicity to normal tissue-derived cells, L-02 and GES-1.
conclusionsWe developed, for the first time, a novel Ad5/35-DKK1-based approach to abrogate Wnt signaling in CSCs and demonstrated that gastric CSC-targeting gene therapy was effective in preclinical experiments.
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