Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice

Abstract Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with ApcMin/+ mice to obtain ma...

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Autores principales:	Lorenzo M. Fernandes, Ahmed Al-Dwairi, Rosalia C. M. Simmen, Meera Marji, Dustin M. Brown, Sarah W. Jewell, Frank A. Simmen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Apc Min Male ApcMin Crypt Depth Villus Length Villus Lamina Propria Medicine R Science Q
Acceso en línea:	https://doaj.org/article/899beda0f140402686c9d2bb53f53cc2
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spelling	oai:doaj.org-article:899beda0f140402686c9d2bb53f53cc22021-12-02T15:08:51ZMalic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice10.1038/s41598-018-32532-w2045-2322https://doaj.org/article/899beda0f140402686c9d2bb53f53cc22018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32532-whttps://doaj.org/toc/2045-2322Abstract Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with ApcMin/+ mice to obtain male ApcMin/+/ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male ApcMin/+/ME1-Tg than ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria. Small intestines of male ApcMin/+/ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/β-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro, but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.Lorenzo M. FernandesAhmed Al-DwairiRosalia C. M. SimmenMeera MarjiDustin M. BrownSarah W. JewellFrank A. SimmenNature PortfolioarticleApc MinMale ApcMinCrypt DepthVillus LengthVillus Lamina PropriaMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Apc Min Male ApcMin Crypt Depth Villus Length Villus Lamina Propria Medicine R Science Q
spellingShingle	Apc Min Male ApcMin Crypt Depth Villus Length Villus Lamina Propria Medicine R Science Q Lorenzo M. Fernandes Ahmed Al-Dwairi Rosalia C. M. Simmen Meera Marji Dustin M. Brown Sarah W. Jewell Frank A. Simmen Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
description	Abstract Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with ApcMin/+ mice to obtain male ApcMin/+/ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male ApcMin/+/ME1-Tg than ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male ApcMin/+ mice. Male ApcMin/+/ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria. Small intestines of male ApcMin/+/ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/β-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro, but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.
format	article
author	Lorenzo M. Fernandes Ahmed Al-Dwairi Rosalia C. M. Simmen Meera Marji Dustin M. Brown Sarah W. Jewell Frank A. Simmen
author_facet	Lorenzo M. Fernandes Ahmed Al-Dwairi Rosalia C. M. Simmen Meera Marji Dustin M. Brown Sarah W. Jewell Frank A. Simmen
author_sort	Lorenzo M. Fernandes
title	Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
title_short	Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
title_full	Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
title_fullStr	Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
title_full_unstemmed	Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice
title_sort	malic enzyme 1 (me1) is pro-oncogenic in apcmin/+ mice
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/899beda0f140402686c9d2bb53f53cc2
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Malic Enzyme 1 (ME1) is pro-oncogenic in ApcMin/+ mice

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