ArticleMolecular oncology2014
Pharmacologic inhibition of vacuolar H+ ATPase reduces physiologic and oncogenic Notch signaling.
Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Disruption of iron metabolism resulting from Dmt1/Slc11a2 deficiency compromises Notch protein degradation and transcriptional activation.The FEBS journal · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Basal Xenobot transcriptomics reveals changes and novel control modality in cells freed from organismal influence.Communications biology · 2025Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity.Nature communications · 2024Article
- The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.Journal of cell science · 2024Article
- V-ATPase Regulates Retinal Progenitor Cell Proliferation During Eye Regrowth inJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- A spatiotemporal Notch interaction map from plasma membrane to nucleus.Science signaling · 2023Article
- Lysosome-mediated chemoresistance in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.Biomolecules · 2021Review
- The HAmerican journal of physiology. Cell physiology · 2021Review
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- Activity of the SNARE Protein SNAP29 at the Endoplasmic Reticulum and Golgi Apparatus.Frontiers in cell and developmental biology · 2021Article
- Notch Transduction in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2020Review
- Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition.International journal of molecular sciences · 2020Review
- Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia.Cancers · 2020Article
- Investigation of Isoform Specific Functions of the V-ATPase a Subunit DuringFrontiers in genetics · 2020Article
- Vacuolar HCells · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling in prominently involved in growth regulation in metazoan tissues. Because of this, Notch is often upregulated in cancer and current efforts point to developing drugs that block its activation. Notch receptor endocytosis towards acidic compartments is a recently appreciated determinant of signaling activation. Vacuolar H(+) ATPase (V-ATPase) is responsible for acidification of endocytic organelles and mutants in V-ATPase subunit encoding genes in model organisms have been recently shown to display loss of Notch signaling. Here, we show that administration of BafilomycinA1 (BafA1), a highly specific V-ATPase inhibitor decreases Notch signaling during Drosophila and Zebrafish development, and in human cells in culture. In normal breast cells, we find that BafA1 treatment leads to accumulation of Notch in the endo-lysosomal system, and reduces its processing and signaling activity. In Notch-addicted breast cancer cells, BafA1 treatment reduces growth in cells expressing membrane tethered forms of Notch, while sparing cells expressing cytoplasmic forms. In contrast, we find that V-ATPase inhibition reduces growth of leukemia cells, without affecting Notch activatory cleavage. However, consistent with the emerging roles of V-ATPase in controlling multiple signaling pathways, in these cells Akt activation is reduced, as it is also the case in BafA1-treated breast cancer cells. Our data support V-ATPase inhibition as a novel therapeutic approach to counteract tumor growth via signaling pathways regulated at the endo-lysosomal level.
Indexed as
Identifiers
What OpenQuestion holds
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.