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RBP4 interferes with tongue squamous cell carcinoma progression by inhibiting the PI3K/AKT signaling pathway and

Ying Yan1, Nan Miao1, Xiaofeng Wang2

  • 1Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Scientific Reports
|February 16, 2026
PubMed

Insights

Retinol-binding protein 4 (RBP4) inhibits tongue squamous cell carcinoma (TSCC) growth by reducing tumor cell proliferation and promoting anti-tumor M1 macrophage polarization. This study reveals RBP4 as a potential therapeutic target for TSCC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Tongue squamous cell carcinoma (TSCC) significantly impacts patient quality of life, necessitating novel therapeutic strategies.
  • Understanding the molecular mechanisms driving TSCC progression and immune evasion is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role and mechanism of retinol-binding protein 4 (RBP4) in TSCC progression.
  • To determine RBP4's effect on tumor-associated macrophage (TAM) polarization and its impact on TSCC growth.

Main Methods:

  • TSCC cell lines with altered RBP4 expression (overexpression and knockdown) were created.
  • Ex vivo experiments assessed RBP4's impact on TSCC cell proliferation and invasion.
  • A co-culture model examined RBP4's influence on macrophage polarization via NF-κB and PI3K/Akt/mTOR signaling pathways.

Main Results:

  • RBP4 overexpression inhibited TSCC cell proliferation and epithelial-mesenchymal transition by reducing PI3K/Akt/mTOR pathway phosphorylation and regulating Snail levels.
  • RBP4 promoted M1-type polarization of tumor-associated macrophages through NF-κB pathway activation.
  • RBP4 demonstrated antitumor effects by inhibiting TSCC growth and migration.

Conclusions:

  • RBP4 inhibits TSCC cell proliferation and migration by suppressing the PI3K-Akt signaling pathway.
  • RBP4 promotes M1-type polarization of TAMs, contributing to their antitumor activity.
  • RBP4 represents a promising therapeutic target for tongue squamous cell carcinoma.
Keywords:
Macrophage polarizationNF-κB signaling pathwayPI3K/Akt signaling pathwayRBP4Tongue squamous cell carcinoma

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