ArticleJournal of experimental & clinical cancer research : CR2019
GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the Hsc70 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.International journal of molecular sciences · 2024Article
- A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.Nature communications · 2024Article
- Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.Archives of toxicology · 2024Article
- Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.Cell death discovery · 2023Article
- New insights into the interplay between autophagy and oxidative and endoplasmic reticulum stress in neuronal cell death and survival.Frontiers in cell and developmental biology · 2022Review
- Nestin is essential for cellular redox homeostasis and gastric cancer metastasis through the mediation of the Keap1-Nrf2 axis.Cancer cell international · 2021Article
- Cascades between miRNAs, lncRNAs and the NF-κB signaling pathway in gastric cancer (Review).Experimental and therapeutic medicine · 2021Review
- A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes.Frontiers in oncology · 2021Article
- Association Between Polymorphisms in Gastric Cancer Related Genes and Risk of Gastric Cancer: A Case-Control Study.Frontiers in molecular biosciences · 2021Article
- RNA Sequencing of Early-Stage Gastric Adenocarcinoma Reveals Multiple Activated Pathways and Novel Long Non-Coding RNAs in Patient Tissue Samples.Reports of biochemistry & molecular biology · 2021Article
- TIPRL, a Novel Tumor Suppressor, Suppresses Cell Migration, and Invasion Through Regulating AMPK/mTOR Signaling Pathway in Gastric Cancer.Frontiers in oncology · 2020Article
- Chaperone Mediated Autophagy Substrates and Components in Cancer.Frontiers in oncology · 2020Review
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Authors and funding
12 authors at 3 institutions in 1 country.
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Abstract
backgroundThe GKN2 is a secretory protein, whose levels decrease in gastric cancer. The present study aimed to investigate the expression, function and mechanism of action of GKN2 in gastric cancer.
methodsMolecular biology assays were performed to elucidate the function and underlying mechanisms of GKN2 in gastric cancer under stress-induced condition in vivo and in vitro. Clinical specimens were used to assess the correlation of GKN2 and prognosis.
resultsWe found that overexpression of GKN2 significantly enhanced apoptosis and growth arrest in vitro. GKN2 expression increased in gastric cancer cells exposed to hydrogen peroxide and promoted reactive oxygen species-induced mitochondrial dysfunction and resulted in increased cell apoptosis via inhibition of NF-κB signaling pathway and activation of JNK signaling pathway through the direct interaction of GKN2 with Hsc70. Trefoil factor 1 might contribute to the tumor suppressing effects of GKN2. MiR-216a downregulated GKN2 expression. GKN2 also inhibited xenograft tumor growth and was an independent and significant prognostic factor for patients with gastric cancer treated with oxaliplatin.
conclusionsTaken together, our data indicate that GKN2 may increase sensitivity of GC cells to the drugs which increase ROS levels in tumors. Inhibition of the interaction between GKN2 and Hsc70 could attenuate the effects induced by GKN2. GKN2 overexpression could be used to determine the subgroup of patients to obtain the more favorable outcome of oxaliplatin treatment and may be used as biomarker of the prognosis of this cancer.
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