Host response as an enhancer of infection-associated cancer and its regulation

2014 Fiscal Year Final Research Report

• Project Area: Conversion of tumor-regulation vector to intercept oncogenic spiral accelerated by infection and inflammation
• Project/Area Number: 22114002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: HATAKEYAMA Masanori 東京大学, 医学(系)研究科(研究院), 教授 (40189551)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Naoko 東京大学, 大学院医学系研究科, 講師 (40279352) ; MUTOH Hiroyuki 自治医科大学, 医学部, 准教授 (50322392) ; TSUTSUMI Ryohei 東京大学, 大学院医学系研究科, 助教 (50435872) ; SAITO Yasuhiro 東京大学, 大学院医学系研究科, 助教 (30613004) ; TAKAHASHI Atsushi 東京大学, 大学院医学系研究科, 助教 (00624496)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: がん / 感染症 / 胃がん / ヘリコバクター・ピロリ / 炎症

Outline of Final Research Achievements

Chronic infection with cagA-positive Helicobacter pylori is causally associated with gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via a bacterial microsyringe, where it acts as an oncogenic scaffold. In this work, we succeeded in solving three dimensional structure of the CagA protein. We also gained insights into the mechanism underlying CagA translocalization across the host plasma membrane. Furthermore, we identified intracellular signaling pathways perturbed by the delivered CagA protein. Using CagA-transgenic mouse model, we found that H. pylori CagA and inflammation mutually reinforce their activities and thereby create a negative spiral that instigates neoplastic transformation of epithelial cells.

Free Research Field

感染腫瘍学、分子腫瘍学