ArticleCarcinogenesis2014
Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺ extrusion, cell migration and survival.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 88 citations in OpenAlex.
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- Single-Cell Analysis with Spatiotemporal Control of Local pH.ACS measurement science au · 2025Article
- The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Neuronal guidance behaviours: the primary cilium perspective.Frontiers in cell and developmental biology · 2025Review
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- Systematic Review of Photodynamic Therapy in Gliomas.Cancers · 2023Review
- IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p/NHE1 axis-mediated regulation of acidic microenvironment.iScience · 2023Article
- Multi-nuclear sodium, diffusion, and perfusion MRI in human gliomas.Journal of neuro-oncology · 2023Article
- Delivery of Melittin as a Lytic Agent via Graphene Nanoparticles as Carriers to Breast Cancer Cells.Journal of functional biomaterials · 2022Article
- Decreased NHE3 expression in colon cancer is associated with DNA damage, increased inflammation and tumor growth.Scientific reports · 2022Article
- The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity.Cancers · 2022Review
- Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.Nanomedicine (London, England) · 2022Article
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- Syngeneic murine glioblastoma models: reactionary immune changes and immunotherapy intervention outcomes.Neurosurgical focus · 2022Article
- Sodium MR Neuroimaging.AJNR. American journal of neuroradiology · 2021Review
- Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism.Cancers · 2021Review
- Calcium carbonate nanoparticles stimulate cancer cell reprogramming to suppress tumor growth and invasion in an organ-on-a-chip system.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Sodium-hydrogen exchanger isoform 1 (NHE1) plays a role in survival and migration/invasion of several cancers and is an emerging new therapeutic target. However, the role of NHE1 in glioblastoma and the interaction of NHE1 expression and function in glioblastoma cells with cytotoxic temozolomide (TMZ) therapy remain unknown. In this study, we detected high levels of NHE1 protein only in primary human glioma cells (GC), glioma xenografts and glioblastoma, but not in human neural stem cells or astrocytes. GC exhibited an alkaline resting pHi (7.46±0.04) maintained by robust NHE1-mediated H(+) extrusion. GC treatment with TMZ for 2-24h triggered a transient decrease in pHi, which recovered by 48h and correlated with concurrent upregulation of NHE1 protein expression. NHE1 protein was colocalized with ezrin at lamellipodia and probably involved in GC migration. The TMZ-treated GC exhibited increased migration and invasion, which was attenuated by addition of NHE1 inhibitor HOE-642. Most importantly, NHE1 inhibition prevented prosurvival extracellular signal-regulated kinase activation and accelerated TMZ-induced apoptosis. Taken together, our study provides the first evidence that GC upregulate NHE1 protein to maintain alkaline pHi. Combining TMZ therapy with NHE1 inhibition suppresses GC migration and invasion, and also augments TMZ-induced apoptosis. These findings strongly suggest that NHE1 is an important cytoprotective mechanism in GC and presents a new therapeutic strategy of combining NHE1 inhibition and TMZ chemotherapy.
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Registered trials
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.