ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2017
Heterodimeric interaction between GKN2 and TFF1 entails synergistic antiproliferative and pro-apoptotic effects on gastric cancer cells.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Coexpression network analysis of gastric adenocarcinoma identifies hub genes as biomarker candidates and their tumor microenvironment associations.Genetics and molecular biology · 2026Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- Role of trefoil factors in maintaining gut health in food animals.Frontiers in veterinary science · 2024Review
- Comprehensive multi-omics analysis identifies chromatin regulator-related signatures and TFF1 as a therapeutic target in lung adenocarcinoma through a 429-combination machine learning approach.Frontiers in immunology · 2024Article
- Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide).International journal of molecular sciences · 2023Article
- Gastrokine 2 Regulates the Antitumor Effect of JAK2/STAT3 Pathway in Gastric Cancer.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Trefoil factor 1 and gastrokine 2 inhibitOncology letters · 2020Article
- Structure, Function, and Therapeutic Potential of the Trefoil Factor Family in the Gastrointestinal Tract.ACS pharmacology & translational science · 2020Review
- Inhibition of GKN2 Attenuates Acute Gastric Lesions Through the NLRP3 Inflammasome.Advances in wound care · 2020Article
- The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions.International journal of molecular sciences · 2020Article
- Multiscale network analysis reveals molecular mechanisms and key regulators of the tumor microenvironment in gastric cancer.International journal of cancer · 2020Article
- Molecular Alterations in the Stomach ofInternational journal of molecular sciences · 2020Article
- GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the Hsc70 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Trefoil Factor Family: Unresolved Questions and Clinical Perspectives.Trends in biochemical sciences · 2019Review
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8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundGKN2 and TFF1 form a heterodimer that is only generated in the mucus-secreting cells of the normal stomach. The formation of this heterodimer is frequently disrupted in gastric cancer. However, the precise roles of GKN2 alone and in the heterodimer with TFF1 as well as the contributions of GKN2 and the heterodimer to gastric carcinogenesis are poorly understood.
methodsCell viability, proliferation, and apoptosis were analyzed in AGS, MKN1, MKN28, and MKN45 gastric cancer cells transfected with GKN2 and/or TFF1 using MTT, BrdU incorporation, and apoptosis assays, respectively. In addition, cell viability was examined in HFE-145 non-neoplastic gastric epithelial cells after GKN2 and/or TFF1 silencing. Furthermore, the cell cycle and the expression of cell cycle and apoptosis related proteins were assessed. The interaction between GKN2 and TFF1 was confirmed by co-immunoprecipitation. Immunohistochemistry was employed to explore TFF1 expression in 169 gastric cancer tissues.
resultsCo-transfection with GKN2 and TFF1 significantly inhibited cell viability and proliferation by inducing G1/S cell cycle arrest and suppressing positive cell cycle regulators. Simultaneous knockdown of GKN2 and TFF1 in HFE-145 cells resulted in markedly increased cell viability. Moreover, the interaction of GKN2 and TFF1 promoted cell death by enhancing caspase-3/7 activity and upregulating pro-apoptotic proteins. At the mRNA level, GKN2 and TFF1 were found to be positively correlated in non-tumor and tumor samples. Immunohistochemistry revealed loss of TFF1 expression in 128 (75.73%) of 169 gastric cancers. There was a borderline-significant association between GKN2 and TFF1 protein expression in gastric cancers (P = 0.0598).
conclusionCollectively, our data demonstrated that the interaction between GKN2 and TFF1 can have synergistic antiproliferative and pro-apoptotic effects on gastric cancer.
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