Cell-surface nucleolin acts as a central mediator for carcinogenic, anti-carcinogenic, and disease-related ligands

Hirota Fujiki1, Tatsuro Watanabe, Masami Suganuma

  • 1Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, 362-0806, Japan, uv4h-fjk@asahi-net.or.jp.

Abstract

Insights

Surface nucleolin acts as a dual receptor, mediating cancer progression with Helicobacter pylori Tipα and inhibiting tumors with anti-HIV peptide HB-19. This highlights its role in both carcinogenesis and cancer prevention.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Immunology

Background:

  • Cell-surface nucleolin functions as a receptor for various ligands.
  • Its interactions are implicated in both disease progression and therapeutic responses.

Purpose of the Study:

  • To review the dual roles of cell-surface nucleolin.
  • To explore its interactions with carcinogenic and anti-carcinogenic ligands.
  • To identify new research avenues for disease prevention.

Main Methods:

  • Investigated the binding of Helicobacter pylori TNF-α-inducing protein (Tipα) and anti-HIV pseudopeptide (HB-19) to cell-surface nucleolin.
  • Utilized nucleolin-targeted siRNA in human gastric cancer cell lines.
  • Assessed tumor development in xenograft nude mouse models.

Main Results:

  • Tipα binding to nucleolin promotes gastric cancer progression by activating NF-κB and gene expression.
  • Nucleolin knockdown inhibited Tipα-induced cell migration and elongation.
  • HB-19 binding to nucleolin demonstrated anti-carcinogenic effects, inhibiting tumor growth in vivo.

Conclusions:

  • Cell-surface nucleolin acts as a carcinogenic mediator for Tipα and an anti-carcinogenic mediator for HB-19.
  • Competition exists between carcinogenic and anti-carcinogenic ligand binding to nucleolin.
  • Interactions with disease-related ligands present a novel research area for ailment prevention and treatment.

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