Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

The tumor necrosis factor-alpha (TNF-alpha)-inducing protein (tip alpha) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tip alpha, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tip alpha is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tip alpha in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tip alpha secreted from H. pylori stimulates gastric cancer development by inducing TNF-alpha, an endogenous tumor promoter, through its interaction with nucleolin, a Tip alpha receptor. This review covers the following topics: tumor-promoting activity of the Tip alpha family members HP-MP1 and Tip alpha, the mechanism underlying this activity of Tip alpha via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tip alpha and N-terminal truncated rTip alpha, inhibition of Tip alpha-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2(/TIS21)), and new strategies to prevent and treat gastric cancer. Thus, Tip alpha contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

Automated summary

Tip alpha, a unique Helicobacter pylori protein, contributes to gastric cancer development by stimulating TNF-α production through interaction with nucleolin. Its presence in American and Euro-Asian strains suggests its involvement in human gastric cancer, different from other pathogenic factors like CagA and VacA.