{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:50:12Z","timestamp":1780073412912,"version":"3.54.0"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["H28"],"award-info":[{"award-number":["H28"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["2016-S"],"award-info":[{"award-number":["2016-S"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Smorking Research Fund","award":["H29-19"],"award-info":[{"award-number":["H29-19"]}]},{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu Cancer Research Fund","doi-asserted-by":"publisher","award":["13-24511"],"award-info":[{"award-number":["13-24511"]}],"id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The tumor necrosis factor-\u03b1 (TNF-\u03b1)-inducing protein (tip\u03b1) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tip\u03b1, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tip\u03b1 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\u03b1 in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tip\u03b1 secreted from H. pylori stimulates gastric cancer development by inducing TNF-\u03b1, an endogenous tumor promoter, through its interaction with nucleolin, a Tip\u03b1 receptor. This review covers the following topics: tumor-promoting activity of the Tip\u03b1 family members HP-MP1 and Tip\u03b1, the mechanism underlying this activity of Tip\u03b1 via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tip\u03b1 and N-terminal truncated rTip\u03b1, inhibition of Tip\u03b1-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2\/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tip\u03b1 contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.<\/jats:p>","DOI":"10.3390\/toxins13030181","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:25:18Z","timestamp":1614594318000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Role of TNF-\u03b1-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-6695","authenticated-orcid":false,"given":"Masami","family":"Suganuma","sequence":"first","affiliation":[{"name":"Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, Faculty of Medicine, Saga University, Nabeshima, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisaburo","family":"Sueoka","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Kyoung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirota","family":"Fujiki","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/S0140-6736(84)91816-6","article-title":"Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration","volume":"1","author":"Marshall","year":"1984","journal-title":"Lancet"},{"key":"ref_2","unstructured":"International Agency for Research on Cancer Working Group on the Evaluation of Carcinogenic Risks to Humans (1994). 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