ArticleOncotarget2015
Acquisition of resistance to trastuzumab in gastric cancer cells is associated with activation of IL-6/STAT3/Jagged-1/Notch positive feedback loop.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 103 citations in OpenAlex.
- Biomarker analysis of the GATSBY study of trastuzumab emtansine versus a taxane in previously treated HER2-positive advanced gastric/gastroesophageal junction cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019Trial
- Lactiplantibacillus Plantarum GUANKE Alleviates Allergic Asthma by Restricting Monocyte-to-DC Differentiation Via Microbiota-Associated IAA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Carvedilol sensitizes paclitaxel-resistant gastric cancer AGS cells to paclitaxel: influences on apoptotic regulators, Notch, PI3K/AKT, ERK1/2 signaling pathways, and miR-34a expression.Medical oncology (Northwood, London, England) · 2025Article
- Review
- Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.Stem cell reviews and reports · 2024Review
- Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin.BMC complementary medicine and therapies · 2023Article
- Prognostic evaluation of pancreatic cancer based on the model of chemo-radiotherapy resistance-related genes.Journal of gastrointestinal oncology · 2023Article
- NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality.Translational oncology · 2023Article
- Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Targeting IKKε in Androgen-Independent Prostate Cancer Causes Phenotypic Senescence and Genomic Instability.Molecular cancer therapeutics · 2022Article
- NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration.Frontiers in cellular and infection microbiology · 2022Article
- Hsa_circ_0017728 as an oncogene in gastric cancer by sponging miR-149 and modulating the IL-6/STAT3 pathway.Archives of medical science : AMS · 2022Article
- The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response.NPJ precision oncology · 2021Article
- Tetraspanins: Novel Molecular Regulators of Gastric Cancer.Frontiers in oncology · 2021Review
- The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications.Frontiers in cardiovascular medicine · 2021Review
- Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study, we demonstrate that prolonged treatment by trastuzumab induced resistance of NCI-N87 gastric cancer cells to trastuzumab. The resistant cells possessed typical characteristics of epithelial to mesenchymal transition (EMT)/cancer stem cells and acquired more invasive and metastatic potentials both in vitro and in vivo. Long term treatment with trastuzumab dramatically inhibited the phosphorylation of Akt, but triggered the activation of STAT3. The level of IL-6 was remarkably increased, implicating that the release of IL-6 that drives the STAT3 activation initiates the survival signaling transition. Furthermore, the Notch activities were significantly enhanced in the resistant cells, companied by upregulation of the Notch ligand Jagged-1 and the Notch responsive genes Hey1 and Hey2. Inhibiting the endogenous Notch pathway reduced the IL-6 expression and restored the sensitivities of the resistant cells to trastuzumab. Blocking of the STAT3 signaling abrogated IL-6-induced Jagged-1 expression, effectively inhibited the growth of the trastuzumab resistant cells, and enhanced the anti-tumor activities of trastuzumab in the resistant cells. These findings implicate that the IL-6/STAT3/Jagged-1/Notch axis may be a useful target and that combination of the Notch or STAT3 inhibitors with trastuzumab may prevent or delay clinical resistance and improve the efficacy of trastuzumab in gastric cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.