ArticleJournal of hematology & oncology2016
A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway.
Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 121 citations in OpenAlex.
- Lactylation-Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterization of acquired capecitabine resistance in MKN-45 gastric cancer cells reveals preserved apoptotic sensitivity.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- Glycolysis‑driven immunosuppression in gastric cancer: Metabolic crosstalk between tumor cells and the immune microenvironment (Review).International journal of oncology · 2026Review
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 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
- Exosome crown proteins are promising markers for liquid biopsy of breast cancer.Frontiers in oncology · 2026Review
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Next-generation sequencing identifies potential mechanisms of primary resistance to trastuzumab-containing therapies in HER2-positive gastric cancer: Analysis based on real-world data and online databases.Human vaccines & immunotherapeutics · 2025Article
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Knockdown of MACC1 expression attenuates colorectal cancer cell glucose metabolism by suppressing GLUT4 membrane translocation.Cancer biomarkers : section A of Disease markers · 2025Article
- LINC01224 promotes the Warburg effect in gastric cancer by activating the miR-486-5p/PI3K axis.In vitro cellular & developmental biology. Animal · 2025Article
- Hyperprogressive disease induced by PD-1 inhibitor monotherapy in lung adenocarcinoma with HER2 exon 20 insertion: report of two cases and review of literature.Discover oncology · 2025Article
- Silencing CDH17 reverses cisplatin resistance in gastric cancer cells by regulating the Warburg effect mediated by the Wnt/β-catenin pathway.American journal of translational research · 2025Article
- Chloroquine Suppresses Colorectal Cancer Progression via Targeting CHKA and PFKM to inhibit the PI3K/AKT Pathway and the Warburg Effect.International journal of biological sciences · 2025Article
- Hsa_circ_0001756 drives gastric cancer glycolysis by increasing the expression and stability of PGK1 mRNA.Frontiers in immunology · 2025Article
- Targeting Glycolysis for Treatment of Breast Cancer Resistance: Current Progress and Future Prospects.International journal of biological sciences · 2025Review
- MACC1 revisited - an in-depth review of a master of metastasis.Biomarker research · 2024Review
- HER2-targeted therapies beyond breast cancer - an update.Nature reviews. Clinical oncology · 2024Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTrastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated with the colon cancer 1 (MACC1) predicted poor prognosis of GC and promoted tumor cells proliferation and invasion. In this study, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 reversed this resistance.
methodsThe effect of trastuzumab and glycolysis inhibitor combination on cell viability, apoptosis, and cell metabolism was investigated in vitro using established trastuzumab-resistant GC cell lines. We assessed the impact of trastuzumab combined with oxamate on tumor growth and metabolism in an established xenograft model of HER2-positive GC cell lines.
resultsHere, we found that MACC1 was significantly upregulated in trastuzumab-resistant cell lines. Besides, downregulation of MACC1 in trastuzumab-resistant cells reversed this resistance. Overexpression of MACC1-induced trastuzumab resistance, enhanced the Warburg effect, and activated the PI3K/AKT signaling pathway, while downregulation of MACC1 presented the opposite effects. Moreover, when the PI3K/AKT signaling pathway was inhibited, the effects of MACC1 on resistance and glycolysis were diminished. Our findings indicated that MACC1 promoted the Warburg effect mainly through the PI3K/AKT signaling pathway, which further enhanced GC cells trastuzumab resistance.
conclusionsOur results indicate that co-targeting of HER2 and the Warburg effect reversed trastuzumab resistance in vitro and in vivo, suggesting that the combination might overcome trastuzumab resistance in MACC1-overexpressed, HER2-positive GC patients.
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