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Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer

Yuqin Li1, Lin Xu2, Xiaolan Lu1

  • 1Department of Gastroenterology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

Digestive Diseases and Sciences
|November 29, 2025
PubMed
Abstract

Insights

Helicobacter pylori (HP) lipopolysaccharide (LPS) boosts gastric cancer by increasing MDM2 expression via the TLR4/MAPK/AP-1 pathway, promoting cell growth and immune suppression. MDM2 is a potential therapeutic target for HP-associated gastric cancer.

Area of Science:

  • Oncology
  • Immunology
  • Microbiology

Background:

  • Helicobacter pylori (HP) lipopolysaccharide (LPS) is a key factor in gastric cancer development, causing chronic inflammation and promoting cell proliferation.
  • While HP LPS has lower endotoxic activity than E. coli LPS, it significantly contributes to gastric cancer progression through unknown pathways.

Purpose of the Study:

  • To elucidate the specific signaling pathways involved in HP LPS-induced gastric cancer progression.
  • To investigate the role of MDM2 in HP LPS-mediated gastric tumorigenesis and immune modulation.

Main Methods:

  • Cell lines (GES-1, HGC-27, MKN-45) were treated with HP and E. coli LPS.
  • Western blotting and luciferase assays assessed MDM2 expression and activity.
  • Cell proliferation, migration, invasion, and regulatory T cell (Treg) infiltration were evaluated.
  • In vivo gastric cancer mouse models were utilized.

Main Results:

  • HP infection and HP LPS increased MDM2 levels in gastric precancerous lesions and cancers.
  • HP LPS upregulated MDM2 expression in gastric cancer cells via the TLR4/MAPK/AP-1 pathway.
  • MDM2 promoted gastric cancer cell proliferation, invasion, and Treg-mediated immunosuppression.

Conclusions:

  • HP LPS enhances MDM2 expression through the TLR4/MAPK/AP-1 signaling cascade.
  • MDM2 plays a crucial role in mediating HP LPS's protumor effects, including proliferation and immune evasion.
  • MDM2 represents a promising therapeutic target for managing HP-associated gastric cancer.
Keywords:
Gastric cancerLipopolysaccharideMDM2Tumorigenesis

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