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Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model

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 Apc(Min/+) mice showed accelerated formation of inte...

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Autores principales: Kawaguchi, Makiko, Yamamoto, Koji, Kanemaru, Ai, Tanaka, Hiroyuki, Umezawa, Kazuo, Fukushima, Tsuyoshi, Kataoka, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356577/
https://www.ncbi.nlm.nih.gov/pubmed/27612426
http://dx.doi.org/10.18632/oncotarget.11863
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author Kawaguchi, Makiko
Yamamoto, Koji
Kanemaru, Ai
Tanaka, Hiroyuki
Umezawa, Kazuo
Fukushima, Tsuyoshi
Kataoka, Hiroaki
author_facet Kawaguchi, Makiko
Yamamoto, Koji
Kanemaru, Ai
Tanaka, Hiroyuki
Umezawa, Kazuo
Fukushima, Tsuyoshi
Kataoka, Hiroaki
author_sort Kawaguchi, Makiko
collection PubMed
description 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 Apc(Min/+) mice showed accelerated formation of intestinal tumors. In this study, we focused on the role of nuclear factor-κB (NF-κB) signaling in the HAI-1 loss-induced tumor susceptibility. In the HAI-1-deficient intestine, inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, were upregulated in normal mucosa. Furthermore, increased nuclear translocation of NF-κB was observed in both normal mucosa and tumor tissues of HAI-1-deficient Apc(Min/+) intestines, and an NF-κB 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-κB, on intestinal HAI-1-deficient Apc(Min/+) mice. Treatment with DHMEQ reduced the formation of intestinal tumors compared with vehicle control in the HAI-1-deficient Apc(Min/+) mice. These results suggested that insufficient HAI-1 function promotes intestinal carcinogenesis by activating NF-κB signaling.
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spelling pubmed-53565772017-03-24 Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model Kawaguchi, Makiko Yamamoto, Koji Kanemaru, Ai Tanaka, Hiroyuki Umezawa, Kazuo Fukushima, Tsuyoshi Kataoka, Hiroaki Oncotarget Research Paper 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 Apc(Min/+) mice showed accelerated formation of intestinal tumors. In this study, we focused on the role of nuclear factor-κB (NF-κB) signaling in the HAI-1 loss-induced tumor susceptibility. In the HAI-1-deficient intestine, inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, were upregulated in normal mucosa. Furthermore, increased nuclear translocation of NF-κB was observed in both normal mucosa and tumor tissues of HAI-1-deficient Apc(Min/+) intestines, and an NF-κB 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-κB, on intestinal HAI-1-deficient Apc(Min/+) mice. Treatment with DHMEQ reduced the formation of intestinal tumors compared with vehicle control in the HAI-1-deficient Apc(Min/+) mice. These results suggested that insufficient HAI-1 function promotes intestinal carcinogenesis by activating NF-κB signaling. Impact Journals LLC 2016-09-06 /pmc/articles/PMC5356577/ /pubmed/27612426 http://dx.doi.org/10.18632/oncotarget.11863 Text en Copyright: © 2016 Kawaguchi et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kawaguchi, Makiko
Yamamoto, Koji
Kanemaru, Ai
Tanaka, Hiroyuki
Umezawa, Kazuo
Fukushima, Tsuyoshi
Kataoka, Hiroaki
Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title_full Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title_fullStr Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title_full_unstemmed Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title_short Inhibition of nuclear factor-κB signaling suppresses Spint1-deletion-induced tumor susceptibility in the Apc(Min/+) model
title_sort inhibition of nuclear factor-κb signaling suppresses spint1-deletion-induced tumor susceptibility in the apc(min/+) model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356577/
https://www.ncbi.nlm.nih.gov/pubmed/27612426
http://dx.doi.org/10.18632/oncotarget.11863
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