ArticlePloS one2014
Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Computational analysis of the structural and functional impact of the deleterious nsSNPs in the humanBiochemistry and biophysics reports · 2026Article
- Shared genetic association between inflammatory bowel disease and acute myeloid leukemia: insights from mendelian randomization and transcriptomic analyses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Role of thrombomodulin expression on hematopoietic stem cells.Journal of thrombosis and haemostasis : JTH · 2020Article
- The Thrombin Receptor Restricts Subventricular Zone Neural Stem Cell Expansion and Differentiation.Scientific reports · 2018Article
- Protease-activated receptor-1 inhibits proliferation but enhances leukemia stem cell activity in acute myeloid leukemia.Oncogene · 2017Article
- PAR1 inhibition suppresses the self-renewal and growth of A2B5-defined glioma progenitor cells and their derived gliomas in vivo.Oncogene · 2016Article
- Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets.Blood cancer journal · 2016Article
- Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.Cancer metastasis reviews · 2015Review
- PAR1 participates in the ability of multidrug resistance and tumorigenesis by controlling Hippo-YAP pathway.Oncotarget · 2015Article
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Authors and funding
10 authors.
Funding
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Abstract
External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.
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