ArticleInternational journal of medical sciences2020
Metabolic pathways underlying GATA6 regulating Trastuzumab resistance in Gastric Cancer cells based on untargeted metabolomics.
Article in International journal of medical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Efficacy and safety of antibody-drug conjugates in HER2-positive and HER2-low advanced gastric cancer: a systematic review and update.Journal of the Egyptian National Cancer Institute · 2026Pooled it
- A study on the mechanism of action of B7H4 in HER2-positive gastric cancer and its sensitivity to trastuzumab therapy.Translational cancer research · 2026Article
- Dual roles of lactylation modification in gastric cancer: Crosstalk between metabolic reprogramming and epigenetic regulation (Review).Oncology reports · 2026Review
- Identification of factors conferring resistance to trastuzumab deruxtecan in advanced gastric cancer: a translational study from the single-arm, phase II, DESTINY-Gastric06 trial.Precision clinical medicine · 2026Article
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Smad4 loss identifies aggressive subtype with immunotherapy and anti-HER-2 treatment resistance in gastric cancer.British journal of cancer · 2025Article
- Review
- HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.Frontiers in immunology · 2025Review
- The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.Cell death discovery · 2024Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Cuproptosis-related genes predict prognosis and trastuzumab therapeutic response in HER2-positive breast cancer.Scientific reports · 2024Article
- Article
- Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis.World journal of gastroenterology · 2023Article
- GATA6-AS1 Regulates Intestinal Epithelial Mitochondrial Functions, and its Reduced Expression is Linked to Intestinal Inflammation and Less Favourable Disease Course in Ulcerative Colitis.Journal of Crohn's & colitis · 2023Article
- Inhibition of PFKFB3 in HER2-positive gastric cancer improves sensitivity to trastuzumab by inducing tumour vessel normalisation.British journal of cancer · 2022Article
- Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches.Pharmaceutics · 2022Review
- Circulatory Metabolomics Reveals the Association of the Metabolites With Clinical Features in the Patients With Intrahepatic Cholestasis of Pregnancy.Frontiers in physiology · 2022Article
- Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.Frontiers in oncology · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trastuzumab has proven its effectiveness in gastric cancer with HER-2 gene-amplification, which has now developed resistance while the mechanism of which is not fully elucidated. Our previous studies demonstrated that the activity of GATA6 binding protein 6 (GATA6) enhanced prominently in trastuzumab resistant gastric cancer cell lines (NCI N87R and MKN45R). In the present study, we further confirmed the re-sensitization to trastuzumab and inhibition of mitochondrial functions of GATA6 knockout sublines (NCI N87R/ΔGATA6 and MKN45R/ΔGATA6). Moreover, we applied untargeted metabolomic profiling to investigate the potential roles of GATA6 in metabolism of NCI N87R and MKN45R. The UPLC system coupled with Q-Exactive Focus Orbitrap mass spectrometry, multivariate in combination with univariate analysis were performed for the screening of differential metabolites between resistant cells and GATA6 knockout sublines. A total of 68 and 59 endogenous metabolites were found to be altered significantly in NCI N87R/ΔGATA6 and MKN45R/ΔGATA6 cells compared with NCI N87R and MKN45R, respectively. Pathway analyses indicated disturbance of metabolic pathways after GATA6 knockout including tricarboxylic acid (TCA) cycle, glycolysis and energy-related amino acid pathways. An integrated proteomics-metabolomics revealed that sub-networks were closely related to TCA cycle, glycolysis, multiple amino acid and nucleotide metabolism. Western blot showed that TCA cycle and glycolysis-related molecules, including PKM, GLS, GLUL and LDHA, were downregulated in GATA6 knockout sublines. Taken together, these findings demonstrate that GATA6 is involved in metabolism reprogramming which might contribute to trastuzumab resistance in gastric cancer.
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