ArticlePNAS nexus2022
The endosomal pH regulator NHE9 is a driver of stemness in glioblastoma.
Article in PNAS nexus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- High-resolution structures of human NHE6 and NHE9 elucidate endosomal ion and lipid interactions.Nature communications · 2026Article
- The Christianson syndrome protein, sodium hydrogen exchanger isoform 6, is required for fat accumulation.The Journal of physiology · 2025Article
- Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer.NPJ systems biology and applications · 2024Article
- A systematic computational analysis of the endosomal recycling pathway in glioblastoma.Biochemistry and biophysics reports · 2024Article
- An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.Molecular cancer research : MCR · 2024Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
A small population of self-renewing stem cells initiate tumors and maintain therapeutic resistance in glioblastoma (GBM). Given the limited treatment options and dismal prognosis for this disease, there is urgent need to identify drivers of stem cells that could be druggable targets. Previous work showed that the endosomal pH regulator NHE9 is upregulated in GBM and correlates with worse survival prognosis. Here, we probed for aberrant signaling pathways in patient-derived GBM cells and found that NHE9 increases cell surface expression and phosphorylation of multiple receptor tyrosine kinases (RTKs) by promoting their escape from lysosomal degradation. Downstream of NHE9-mediated receptor activation, oncogenic signaling pathways converged on the JAK2-STAT3 transduction axis to induce pluripotency genes Oct4 and Nanog and suppress markers of glial differentiation. We used both genetic and chemical approaches to query the role of endosomal pH in GBM phenotypes. Loss-of-function mutations in NHE9 that failed to alkalinize endosomal lumen did not increase self-renewal capacity of gliomaspheres in vitro. However, monensin, a chemical mimetic of Na
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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.