KLF4 deletion alters gastric cell lineage and induces MUC2 expression

Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a...

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Autores principales: Yu, T, Chen, X, Lin, T, Liu, J, Li, M, Zhang, W, Xu, X, Zhao, W, Liu, M, Napier, D L, Wang, C, Evers, B M, Liu, C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143387/
https://www.ncbi.nlm.nih.gov/pubmed/27277677
http://dx.doi.org/10.1038/cddis.2016.158
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author Yu, T
Chen, X
Lin, T
Liu, J
Li, M
Zhang, W
Xu, X
Zhao, W
Liu, M
Napier, D L
Wang, C
Evers, B M
Liu, C
author_facet Yu, T
Chen, X
Lin, T
Liu, J
Li, M
Zhang, W
Xu, X
Zhao, W
Liu, M
Napier, D L
Wang, C
Evers, B M
Liu, C
author_sort Yu, T
collection PubMed
description Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4(fl/fl) and Lgr5-Cre;Klf4(fl/fl). KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis.
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spelling pubmed-51433872016-12-23 KLF4 deletion alters gastric cell lineage and induces MUC2 expression Yu, T Chen, X Lin, T Liu, J Li, M Zhang, W Xu, X Zhao, W Liu, M Napier, D L Wang, C Evers, B M Liu, C Cell Death Dis Original Article Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4(fl/fl) and Lgr5-Cre;Klf4(fl/fl). KLF4 was deleted by Rosa-Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis. Nature Publishing Group 2016-06 2016-06-09 /pmc/articles/PMC5143387/ /pubmed/27277677 http://dx.doi.org/10.1038/cddis.2016.158 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Yu, T
Chen, X
Lin, T
Liu, J
Li, M
Zhang, W
Xu, X
Zhao, W
Liu, M
Napier, D L
Wang, C
Evers, B M
Liu, C
KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title_full KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title_fullStr KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title_full_unstemmed KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title_short KLF4 deletion alters gastric cell lineage and induces MUC2 expression
title_sort klf4 deletion alters gastric cell lineage and induces muc2 expression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143387/
https://www.ncbi.nlm.nih.gov/pubmed/27277677
http://dx.doi.org/10.1038/cddis.2016.158
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