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Updated: Jun 1, 2026

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
10:28

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

c-Met signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype

Yunqing Li1, Angela Li, Martin Glas

  • 1Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA. LiYu@kennedykrieger.org

Proceedings of the National Academy of Sciences of the United States of America
|June 2, 2011
PubMed

Insights

The tyrosine kinase c-Met promotes glioblastoma stem cell (GBM SC) growth and survival. c-Met signaling, through Nanog, maintains GBM SC stemness and self-renewal, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology
  • Molecular Signaling

Background:

  • The tyrosine kinase c-Met is implicated in cancer progression and resistance to therapy.
  • c-Met hyperactivation is linked to tumor-initiating stem cells, but its role in neoplastic stem cell formation is unknown.
  • Glioblastoma (GBM) is an aggressive brain tumor with a population of tumor-initiating stem cells.

Purpose of the Study:

  • To investigate the role of c-Met signaling in the formation and maintenance of glioblastoma stem cells (GBM SCs).
  • To identify the molecular mechanisms by which c-Met influences GBM SC properties.

Main Methods:

  • Analysis of c-Met activation and expression in glioblastoma neurospheres and clinical specimens.
  • Assessment of c-Met's effect on stem cell marker expression and phenotype.
  • Investigation of c-Met's impact on reprogramming transcription factors (RFs) and differentiation.
  • Evaluation of Nanog's role in mediating c-Met's effects on GBM SCs.

Main Results:

  • c-Met is activated and functional in GBM neurospheres enriched for stem cells.
  • c-Met expression/function correlates with stem cell markers and the neoplastic stem cell phenotype.
  • c-Met activation induces reprogramming factors and counteracts differentiation in GBM neurospheres.
  • Nanog mediates c-Met's induction of neurosphere formation and self-renewal.

Conclusions:

  • c-Met signaling plays a crucial role in maintaining the glioblastoma stem cell population.
  • The mechanism involves c-Met-induced expression of Nanog and potentially other reprogramming factors.
  • Targeting c-Met may represent a therapeutic strategy to deplete GBM stem cells.

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