| First Author | Kawaguchi M | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 42 | Pages | 68614-68622 |
| PubMed ID | 27612426 | Mgi Jnum | J:310031 |
| Mgi Id | MGI:6761024 | Doi | 10.18632/oncotarget.11863 |
| Citation | Kawaguchi M, et al. (2016) Inhibition of nuclear factor-kappaB signaling suppresses Spint1-deletion-induced tumor susceptibility in the ApcMin/+ model. Oncotarget 7(42):68614-68622 |
| abstractText | Hepatocyte growth factor activator inhibitor type 1 (HAI-1), encoded by the Spint1 gene, is a membrane-bound serine protease inhibitor expressed on the epithelial cell surface. We have previously reported that the intestine-specific Spint1-deleted ApcMin/+ mice showed accelerated formation of intestinal tumors. In this study, we focused on the role of nuclear factor-kappaB (NF-kappaB) signaling in the HAI-1 loss-induced tumor susceptibility. In the HAI-1-deficient intestine, inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, were upregulated in normal mucosa. Furthermore, increased nuclear translocation of NF-kappaB was observed in both normal mucosa and tumor tissues of HAI-1-deficient ApcMin/+ intestines, and an NF-kappaB target gene, such as urokinase-type plasminogen activator, was upregulated in the HAI-1-deficient tumor tissues. Thus, we investigated the effect of dehydroxymethylepoxyquinomicin (DHMEQ), a synthetic inhibitor of NF-kappaB, on intestinal HAI-1-deficient ApcMin/+ mice. Treatment with DHMEQ reduced the formation of intestinal tumors compared with vehicle control in the HAI-1-deficient ApcMin/+ mice. These results suggested that insufficient HAI-1 function promotes intestinal carcinogenesis by activating NF-kappaB signaling. |
