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Cross Interaction between M2 Muscarinic Receptor and Notch1/EGFR Pathway in Human Glioblastoma Cancer Stem Cells: Effects on Cell Cycle Progression and Survival.

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  • معلومة اضافية
    • المصدر:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Basel, Switzerland : MDPI
    • الموضوع:
      Signal Transduction*/drug effects; Cell Cycle/*physiology ; Cell Proliferation/*physiology ; Glioblastoma/*pathology ; Receptor, Muscarinic M2/*metabolism ; Receptor, Notch1/*metabolism; Brain Neoplasms/genetics ; Cell Division/physiology ; Cell Line, Tumor ; ErbB Receptors/metabolism ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Humans ; Neoplastic Stem Cells/pathology ; Receptor, Muscarinic M2/genetics
    • نبذة مختصرة :
      Glioblastomas (GBM) are the most aggressive form of primary brain tumors in humans. A key feature of malignant gliomas is their cellular heterogeneity. In particular, the presence of an undifferentiated cell population of defined Glioblastoma Stem cells (GSCs) was reported. Increased expression of anti-apoptotic and chemo-resistance genes in GCSs subpopulation favors their high resistance to a broad spectrum of drugs. Our previous studies showed the ability of M2 muscarinic receptors to negatively modulate the cell growth in GBM cell lines and in the GSCs. The aim of this study was to better characterize the inhibitory effects of M2 receptors on cell proliferation and survival in GSCs and investigate the molecular mechanisms underlying the M2-mediated cell proliferation arrest and decreased survival. Moreover, we also evaluated the ability of M2 receptors to interfere with Notch1 and EGFR pathways, whose activation promotes GSCs proliferation. Our data demonstrate that M2 receptors activation impairs cell cycle progression and survival in the primary GSC lines analyzed (GB7 and GB8). Moreover, we also demonstrated the ability of M2 receptor to inhibit Notch1 and EGFR expression, highlighting a molecular interaction between M2 receptor and the Notch-1/EGFR pathways also in GSCs.
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    • Contributed Indexing:
      Keywords: EGFR; M2 muscarinic receptors; Notch; apoptosis; cancer stem cells; cell cycle
    • الرقم المعرف:
      0 (NOTCH1 protein, human)
      0 (Receptor, Muscarinic M2)
      0 (Receptor, Notch1)
      EC 2.7.10.1 (EGFR protein, human)
      EC 2.7.10.1 (ErbB Receptors)
    • الموضوع:
      Date Created: 20200319 Date Completed: 20210316 Latest Revision: 20210316
    • الموضوع:
      20221213
    • الرقم المعرف:
      PMC7140674
    • الرقم المعرف:
      10.3390/cells9030657
    • الرقم المعرف:
      32182759