ArticleOncoTargets and therapy2021
Daam1 Overexpression Promotes Gastric Cancer Progression and Regulates ERK and AKT Signaling Pathways.
Article in OncoTargets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Review
- Review
- Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer.Cancer cell international · 2025Article
- Mendelian Randomization Integrating GWAS and eQTL Data Reveals DAAM1, a Potential Immune-Related Biomarker for Breast Cancer Prognosis.Breast cancer (Dove Medical Press) · 2025Article
- Mesenchymal Stem Cells Accelerate Recovery of Acetic Acid-Induced Chronic Gastric Ulcer by Regulating Ekt/Akt/TRIM29 Axis.Stem cells international · 2024Article
- Dishevelled-Associated Activator of Morphogenesis 2 (DAAM2) Predicts the Immuno-Hot Phenotype in Pancreatic Adenocarcinoma.Frontiers in molecular biosciences · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
objectiveThe dishevelled-associated activator of morphogenesis 1 (DAAM1) has been reported to be closely associated with human cancers. However, its involvement in human gastric cancer (GC) remains largely unexplored. This study aimed to investigate the clinical significance and biological roles of Daam1 in human GC.
methodsDaam1 protein expression was examined in 124 cases of gastric adenocarcinomas using immunohistochemistry. Daam1 plasmid and siRNA transfection were carried out in SGC7901 and AGS cell lines. CCK-8, colony formation, Annexin V/PI, JC-1 staining, and Western blotting were used to explore the biological functions and potential underlying mechanisms of Daam1 in GC cells.
resultsOur results showed that Daam1 was overexpressed in GC specimens. A high Daam1 level was associated with tumor-node-metastasis (TNM) stage, T status, nodal metastasis, and poor patient survival. Analysis of the Oncomine dataset revealed upregulation of Daam1 mRNA in GC tissues. Western blot showed that Daam1 protein expression was higher in GC cell lines compared to the normal GES-1 cell line. CCK-8 and colony formation assays showed that ectopic Daam1 expression upregulated the cell growth rate and colony number in SGC-7901 cells, while Daam1 siRNA knockdown downregulated the growth rate and colony number in AGS cells. CCK-8 and Annexin V/PI apoptosis assays demonstrated that Daam1 overexpression decreased cisplatin sensitivity and downregulated cisplatin-induced apoptosis. JC1 staining showed that Daam1 overexpression upregulated, while Daam1 depletion downregulated mitochondrial membrane potential. Mechanistically, Daam1 overexpression downregulated p21 and upregulated p-ERK and p-AKT. The increased proliferation rate and decreased cisplatin sensitivity/apoptosis induced by ectopic Daam1 were reversed after treatment with AKT and ERK inhibitors.
conclusionTaken together, our results showed that Daam1 overexpression was associated with poor prognosis and promoted malignant activity via regulation of ERK and AKT pathways in GC cells, indicating Daam1 is a malignant biomarker and potential therapeutic target in GC.
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