Academic Journal

Upregulation of Epithelial-To-Mesenchymal Transition Markers and P2X7 Receptors Is Associated to Increased Invasiveness Caused by P2X7 Receptor Stimulation in Human Glioblastoma Stem Cells

التفاصيل البيبلوغرافية
العنوان: Upregulation of Epithelial-To-Mesenchymal Transition Markers and P2X7 Receptors Is Associated to Increased Invasiveness Caused by P2X7 Receptor Stimulation in Human Glioblastoma Stem Cells
المؤلفون: Sihana Ziberi, Mariachiara Zuccarini, Marzia Carluccio, Patricia Giuliani, Lucia Ricci-Vitiani, Roberto Pallini, Francesco Caciagli, Patrizia Di Iorio, Renata Ciccarelli
المصدر: Cells, Vol 9, Iss 1, p 85 (2019)
بيانات النشر: MDPI AG, 2019.
سنة النشر: 2019
المجموعة: LCC:Cytology
مصطلحات موضوعية: glioblastoma stem cells (gscs), epithelial-to-mesenchymal transition (emt) markers, gsc invasiveness, transforming growth factor beta, bzatp, p2x7 receptor splice variants a and b, Cytology, QH573-671
الوصف: Glioblastoma (GBM) stem cells (GSCs), which contribute to GBM unfavorable prognosis, show high expression levels of ATP/P2X7 receptors (P2X7R). Here, we reported that cells exposure to 2’(3’)-O-(4-benzoylbenzoyl)-ATP (BzATP), a P2X7R agonist, up-regulated the expression of markers associated to epithelial-to-mesenchymal transition (EMT), a process likely contributing to GSC malignancy, and increased GSC migration/invasiveness like the known EMT inducer, Transforming Growth Factor β1 (TGFβ1). These effects were coupled to phosphorylation of SMAD2, a downstream effector in the TGFβ pathway, suggesting its involvement in P2X7R-mediated activity in GSCs. All BzATP effects, including a decrease in the caspase 3/7 activity in GSC medium, were mostly counteracted by the P2X7R antagonist A438079. Finally, BzATP increased the subunit expression of two main human P2X7R splice variants, the full-length P2X7A and the truncated P2X7B, lacking the carboxylic tail, which have different functional properties depending on their arrangement. Since up-regulation of A/B subunits might favor their assembly into a heterotrimeric P2X7R with great sensitivity towards agonists and cell energy support, this is in line with increased EMT markers expression, cell migration/invasion and GSC survival observed following P2X7R stimulation. As in GBM microenvironment extracellular ATP levels may activate P2X7R, our data suggest a P2X7R role in GBM recurrence/invasiveness.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2073-4409
Relation: https://www.mdpi.com/2073-4409/9/1/85; https://doaj.org/toc/2073-4409
DOI: 10.3390/cells9010085
URL الوصول: https://doaj.org/article/375d69bbfba841d1ae6180d025efc026
رقم الانضمام: edsdoj.375d69bbfba841d1ae6180d025efc026
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20734409
DOI:10.3390/cells9010085