ArticleBiochimica et biophysica acta. Molecular cell research2018
Prazosin induced lysosomal tubulation interferes with cytokinesis and the endocytic sorting of the tumour antigen CD98hc.
Article in Biochimica et biophysica acta. Molecular cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 8 citations in OpenAlex.
- Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.Stem cell reports · 2026Article
- The Discovery of α-Adrenoceptor Antagonists as a Potential New Treatment Option for Uveal Melanoma.Biomolecules · 2025Article
- Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Comprehensive analysis of disulfidptosis-related genes and the immune microenvironment in heart failure.Frontiers in cell and developmental biology · 2024Article
- Development of a high affinity AnticalinTheranostics · 2020Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
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Abstract
The quinazoline based drug prazosin (PRZ) is a potent inducer of apoptosis in human cancer cells. We recently reported that PRZ enters cells via endocytosis and induces tubulation of the endolysosomal system. In a proteomics approach aimed at identifying potential membrane proteins with binding affinity to quinazolines, we detected the oncoprotein CD98hc. We confirmed shuttling of CD98hc towards lysosomes and upregulation of CD98hc expression in PRZ treated cells. Gene knockout (KO) experiments revealed that endocytosis of PRZ still occurs in the absence of CD98hc - suggesting that PRZ does not enter the cell via CD98hc but misroutes the protein towards tubular lysosomes. Lysosomal tubulation interfered with completion of cytokinesis and provoked endoreplication. CD98hc KO cells showed reduced endoreplication capacity and lower sensitivity towards PRZ induced apoptosis than wild type cells. Thus, loss of CD98hc does not affect endocytosis of PRZ and lysosomal tubulation, but the ability for endoreplication and survival of cells. Furthermore, we found that glutamine, lysomototropic agents - namely chloroquine and NH
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