Nucleolin promotes TGF-β signaling initiation via TGF-β receptor I in glioblastoma

Shunzeng Lv1,2, Jie Zhang1,3, Mingzhi Han2

  • 1Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Insights

Cell surface nucleolin interacts with TGF-β receptor I, promoting glioblastoma growth. Blocking nucleolin or TβR-I inhibits cancer cell signaling and proliferation, identifying nucleolin as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The transforming growth factor β (TGF-β) pathway is crucial in advanced cancer oncogenesis.
  • Cell surface nucleolin's role in TGF-β pathway activation, particularly in glioblastoma, remains unclear.

Purpose of the Study:

  • To investigate the effect of cell surface nucleolin on the TGF-β pathway in glioblastoma.
  • To determine if nucleolin is a potential therapeutic target for glioblastoma.

Main Methods:

  • Antibodies targeting nucleolin and TGF-β receptor I (TβR-I) were used to block pathways.
  • Nucleolin siRNA was employed for gene knockdown studies.
  • Immunoprecipitation was performed to confirm protein interactions.
  • Cellular assays including wound-healing, soft-agar, and MTT were conducted.

Main Results:

  • Blocking nucleolin or TβR-I inhibited phosphorylation of CrkL, Erk1/2, and Smad2.
  • Nucleolin knockdown suppressed the expression of p-CrkL, p-Erk1/2, and p-Smad2.
  • Direct interaction between cell surface nucleolin and TβR-I was observed on U87 cell membranes.
  • Nucleolin knockdown significantly impaired U87 cell wound closure, colony formation, and overall growth.

Conclusions:

  • Cell surface nucleolin promotes and regulates the TGF-β pathway by interacting with TβR-I.
  • Nucleolin is essential for the initiation and activation of TGF-β signaling in glioblastoma.
  • Nucleolin represents a potential therapeutic target for glioblastoma treatment.

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