ArticleJournal of experimental & clinical cancer research : CR2018
Elevated Na/H exchanger 1 (SLC9A1) emerges as a marker for tumorigenesis and prognosis in gliomas.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- mRNA markers for survival prediction in glioblastoma multiforme patients: a systematic review with bioinformatic analyses.BMC cancer · 2024Pooled it
- LILRB3 inhibition reverses immunosuppression in glioma: a nanoparticle-based therapeutic strategy.Journal of nanobiotechnology · 2026Article
- NHE1-Mediated Metabolic Reprogramming in Cancer.Metabolites · 2026Review
- The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Targeting glioma-associated microglia and macrophages: a new frontier in glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- Deciphering Mitochondria: Unveiling Their Roles in Mechanosensing and Mechanotransduction.Research (Washington, D.C.) · 2025Review
- Machine learning-driven SLC prognostic signature for glioma: predicting survival and immunotherapy response.Frontiers in pharmacology · 2025Article
- Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3.Cell death discovery · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Acid-base transporters in the context of tumor heterogeneity.Pflugers Archiv : European journal of physiology · 2024Review
- Hexamethylene amiloride synergizes with venetoclax to induce lysosome-dependent cell death in acute myeloid leukemia.iScience · 2024Article
- Warburg effect-related risk scoring model to assess clinical significance and immunity characteristics of glioblastoma.Cancer medicine · 2023Article
- Downregulating NHE-1 decreases the apoptosis of hippocampal cells in epileptic model rats based on the NHE-1/calpain1 pathway.Heliyon · 2023Article
- CD44 is a potential immunotherapeutic target and affects macrophage infiltration leading to poor prognosis.Scientific reports · 2023Article
- Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review.International journal of molecular sciences · 2023Review
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- Targeting Na-H exchanger 1 overcomes nuclear factor kappa B-mediated tumor resistance to radiotherapy.Neoplasia (New York, N.Y.) · 2023Article
- Review
- The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity.Cancers · 2022Review
- Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes.Neurosurgical focus · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundSodium/hydrogen exchanger 1 (NHE1), encoded by the SLC9A1 gene (SoLute Carrier family 9A1) in humans, is the main H
methodsThe Chinese Glioma Genome Atlas (CGGA) dataset containing transcriptome sequencing data of 325 glioma samples and the Cancer Genome Atlas (TCGA) with 698 glioma mRNAseq data were analyzed in this study. Mouse SB28 and GL26 intracranial syngeneic glioma models in C57BL/6 J mice were established to investigate NHE1 expression and impact of NHE1 protein inhibition with its inhibitor HOE642 on tumorigenesis and anti-PD1 therapy. Tumor angiogenesis, immunogenicity, and progression were assessed by immunofluorescence staining and flow cytometric profiling.
resultsAnalysis of SLC9A1 mRNA expression in two data sets, CGGA and TCGA, reveals significantly higher SLC9A1 mRNA levels in higher grade gliomas. The SLC9A1 mRNA expression was especially enriched in isocitrate dehydrogenase (IDH)1/2 wild-type glioblastoma (GBM) and in mesenchymal glioma subtypes. Worsened survival probabilities were correlated with the elevated SLC9A1 mRNA levels in gliomas. The underlying mechanisms include promoting angiogenesis, and extracellular matrix remodeling. Increased SLC9A1 mRNA expression was also associated with tumor-associated macrophage accumulation. NHE1 inhibitor HOE642 reduced glioma volume, invasion, and prolonged overall survival in mouse glioma models. Blockade of NHE1 protein also stimulated immunogenic tumor microenvironment via activating CD8 T-cell accumulation, increasing expression of interferon-gamma (Ifng), and sensitized animals to anti-PD-1 therapy.
conclusionOur findings strongly suggest that NHE1 protein emerges as a marker for tumorigenesis and prognosis in glioma. Blocking NHE1 protein is a novel strategy for adjuvant anti-cancer therapies.
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