ArticleJournal of translational medicine2023
Hepatocyte SGK1 activated by hepatic ischemia-reperfusion promotes the recurrence of liver metastasis via IL-6/STAT3.
Article in Journal of translational medicine, 2023. 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, 35 citations in OpenAlex.
- Review
- Characterizing risk groups in papillary thyroid carcinoma through T-Cell mediated tumor cell killing-related genes: a pathway to therapeutic predictions.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Redefining Liver Transplantation Indications for Hepatic Malignancies in the Era of Precision Transplant Oncology: An Up-to-Date Narrative Review.Journal of clinical medicine · 2026Review
- Cytokines and Chemokines as Emerging Biomarkers and Therapeutic Targets in Colorectal Cancer-Narrative Review.International journal of molecular sciences · 2026Review
- Oxidized Phospholipids Aggravate Hepatic Ischemia/Reperfusion Injury by Promoting Macrophage M1 Polarization Via Regulating the Wnt/β-catenin/Autophagy Axis.Inflammation · 2026Article
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- SLC2A3 Expression is Differentially Associated with Postoperative Recurrence, Complications, and Liver Metastasis in Colorectal Cancer.Cancer management and research · 2026Article
- Neutrophil extracellular traps: the hidden driver of gastrointestinal cancer and emerging therapeutic strategies.Frontiers in immunology · 2026Review
- Liver ischemia-reperfusion promotes tumor metastasis via neutrophil-endothelial interactions: targeting ICAM1 to prevent metastatic recurrence.Journal of translational medicine · 2025Article
- Mycl, activated by Sgk1-phosphorylated Stat3, mediates osteoclastogenesis via Ctsk transcriptional regulation.Scientific reports · 2025Article
- Proteomic Landscape of Colorectal Cancer Derived Liver Metastasis Reveals Three Distinct Phenotypes With Specific Signaling and Enhanced Survival.Molecular & cellular proteomics : MCP · 2025Article
- Mechanism of miR-107/HMOX1 axis in hepatic sinusoidal endothelial cells stimulated by ischemia-reperfusion injury.Hereditas · 2025Article
- Neutrophil extracellular traps in cancer: From mechanisms to treatments.Clinical and translational medicine · 2025Review
- Hepatic Stellate Cells Functional Heterogeneity in Liver Cancer.Seminars in liver disease · 2025Review
- Review
- Mfsd2a suppresses colorectal cancer progression and liver metastasis via the S100A14/STAT3 axis.Journal of translational medicine · 2025Article
- Lactate modulates the function of myeloid-derived suppressor cells via Ten-Eleven-Translocation-2-mediated demethylation of glucocorticoid-inducible kinase 1 in lung cancer model.Frontiers in cell and developmental biology · 2025Article
- SYK promotes the formation of neutrophil extracellular traps by inducing PKM2 nuclear translocation and promoting STAT3 phosphorylation to exacerbate hepatic ischemia-reperfusion injury and tumor recurrence.Molecular medicine (Cambridge, Mass.) · 2024Article
- Pancreatectomy Induces Cancer-Promoting Neutrophil Extracellular Traps.Annals of surgical oncology · 2024Article
- Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis.Journal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Surgical resection of the liver metastases increases the incidence of long-term survival in patients with colorectal liver metastasis (CRLM). However, many patients experience CRLM recurrence after the initial liver resection. As an unavoidable pathophysiological process in liver surgery, liver ischemia-reperfusion (IR) injury increases the risk of tumor recurrence and metastasis.
methodsColorectal liver metastasis (CRLM) mouse models and mouse liver partial warm ischemia models were constructed. The levels of lipid peroxidation were detected in cells or tissues. Western Blot, qPCR, elisa, immunofluorescence, immunohistochemistry, scanning electron microscope, flow cytometry analysis were conducted to evaluate the changes of multiple signaling pathways during CRLM recurrence under liver ischemia-reperfusion (IR) background, including SGK1/IL-6/STAT3, neutrophil extracellular traps (NETs) formation, polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) infiltration.
resultsHepatocyte serum/glucocorticoid regulated kinase 1 (SGK1) was activated in response to hepatic ischemia-reperfusion injury to pass hepatocyte STAT3 phosphorylation and serum amyloid A (SAA) hyperactivation signals in CRLM-IR mice, such regulation is dependent on SGK-activated IL-6 autocrine. Administration of the SGK1 inhibitor GSK-650394 further reduced ERK-related neutrophil extracellular traps (NETs) formation and polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) infiltration compared with targeting hepatocyte SGK1 alone, thereby alleviating CRLM in the context of IR.
conclusionsOur study demonstrates that hepatocyte and immune cell SGK1 synergistically promote postoperative CRLM recurrence in response to hepatic IR stress, and identifies SGK1 as a translational target that may improve postoperative CRLM recurrence.
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