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

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