ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
Mitochondrial GRIM-19 deficiency facilitates gastric cancer metastasis through oncogenic ROS-NRF2-HO-1 axis via a NRF2-HO-1 loop.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Research on the mechanism of GRIM-19 affecting lung adenocarcinoma through regulating MDM2 and EMT pathways.Cytotechnology · 2025Article
- ROS Regulate Rotenone-induced SH-SY5Y Dopamine Neuron Death Through Ferroptosis-mediated Autophagy and Apoptosis.Molecular neurobiology · 2025Article
- Prokaryotic organelle mitochondria drive tumorigenesis: "the original sin".Frontiers in oncology · 2025Review
- Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-кB Signaling.Journal of clinical and translational hepatology · 2024Article
- Energy metabolism: a new target for gastric cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Article
- Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties.Antioxidants (Basel, Switzerland) · 2023Review
- LINC00240 in the 6p22.1 risk locus promotes gastric cancer progression through USP10-mediated DDX21 stabilization.Journal of experimental & clinical cancer research : CR · 2023Article
- GRIM-19 in asthenozoospermia regulates GC-2 spd cell proliferation, apoptosis and migration.Scientific reports · 2023Article
- Role of Nrf2 Nucleus Translocation in Beauvericin-Induced Cell Damage in Rat Hepatocytes.Toxins · 2022Article
- Article
- Abnormal methylation in theQRB discovery · 2022Article
- Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/βCancer communications (London, England) · 2021Article
- Review
- Clinical Significance of Heme Oxygenase 1 in Tumor Progression.Antioxidants (Basel, Switzerland) · 2021Review
- [Mechanism of hepatocyte mitochondrial NDUFA13 deficiency-induced liver fibrogenesis: the role of abnormal hepatic stellate cell activation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Upregulation of Linc-ROR Promotes the Proliferation, Migration, and Invasion of Gastric Cancer Cells Through miR-212-3p/FGF7 Axis.Cancer management and research · 2021Article
- Cross-Talk between Oxidative Stress and mOxidative medicine and cellular longevity · 2021Review
- Antidiabetic DPP-4 Inhibitors Reprogram Tumor Microenvironment That Facilitates Murine Breast Cancer Metastasis Through Interaction With Cancer CellsFrontiers in oncology · 2021Article
- Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 AxisFrontiers in oncology · 2021Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundNRF2, a prime target of cellular defense against oxidative stress, has shown a dark side profile in cancer progression. GRIM-19, an essential subunit of the mitochondrial MRC complex I, was recently identified as a suppressive role in tumorigenesis of human gastric cancer (GC). However, little information is available on the role of GRIM-19 and its cross-talk with NRF2 in GC metastasis.
methodsOnline GC database was used to investigate DNA methylation and survival outcomes of GRIM-19. CRISPR/Cas9 lentivirus-mediated gene editing, metastasis mice models and pharmacological intervention were applied to investigate the role of GRIM-19 deficiency in GC metastasis. Quantitative RT-PCR, FACS, Western blot, IHC, IF and reporter gene assay were performed to explore underlying mechanisms.
resultsLow GRIM-19 is correlated with poor survival outcome of GC patients while DNA hypermethylation is associated with GRIM-19 downregulation. GRIM-19 deficiency facilitates GC metastasis and triggers aberrant oxidative stress as well as ROS-dependent NRF2-HO-1 activation. Experimental interventions of specific ROS, NRF2 or HO-1 inhibitor significantly abrogate GRIM-19 deficiency-driven GC metastasis in vitro and in vivo. Moreover, HO-1 inhibition not only reverses GRIM-19 deficiency-driven NRF2 activation, but also feedback blocks NRF2 activator-induced NRF2 signaling, resulting in decreased metastasis-associated genes.
conclusionsOur data suggest that GRIM-19 deficiency accelerates GC metastasis through the oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into the role of oncogenic NRF2 in tumor progression, but also provides new strategies to alleviate the dark side of NRF2 by targeting HO-1.
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