| Budget Amount *help |
¥184,080,000 (Direct Cost: ¥141,600,000、Indirect Cost: ¥42,480,000)
Fiscal Year 2020: ¥28,990,000 (Direct Cost: ¥22,300,000、Indirect Cost: ¥6,690,000)
Fiscal Year 2019: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000)
Fiscal Year 2018: ¥27,300,000 (Direct Cost: ¥21,000,000、Indirect Cost: ¥6,300,000)
Fiscal Year 2017: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2016: ¥53,820,000 (Direct Cost: ¥41,400,000、Indirect Cost: ¥12,420,000)
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| Outline of Final Research Achievements |
Upon delivery into gastric epithelial cells, H. pylori oncoprotein CagA interacts with host proteins such as SHP2 and PAR1b, thereby inducing abnormal mitogenic signals while disrupting epithelial apical-basal polarity to make tumor microenvironment. CagA-mediated inhibition of PAR1b additionally provokes BRCA1 insufficiency that gives rise to DNA double-strand breaks (DSBs) and activates Hippo signaling that prevents apoptosis of DSB cells (= CagA-dependent cancer-inducing stages). As a result, CagA-induced DSBs are repaired by error-prone non-homologous mechanisms, making excess accumulation of genetic mutations including TP53, which underlies generation of cancer cells that do not require H. pylori CagA for the maintenance of their carcinogenic properties (= CagA-independent cancer-inducing stages). The findings elucidate molecular mechanism underpinning the “Hit-and-Run carcinogenesis”.
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