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NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()

NHERF1/EBP50, an adaptor molecule that interacts with β-catenin, YAP, and PTEN, has been recently implicated in the progression of various human malignancies, including colorectal cancer. We report here that NHERF1 acts as a tumor suppressor in vivo for intestinal adenoma development. NHERF1 is high...

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Autores principales: Georgescu, Maria-Magdalena, Gagea, Mihai, Cote, Gilbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018097/
https://www.ncbi.nlm.nih.gov/pubmed/27566107
http://dx.doi.org/10.1016/j.neo.2016.07.003
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author Georgescu, Maria-Magdalena
Gagea, Mihai
Cote, Gilbert
author_facet Georgescu, Maria-Magdalena
Gagea, Mihai
Cote, Gilbert
author_sort Georgescu, Maria-Magdalena
collection PubMed
description NHERF1/EBP50, an adaptor molecule that interacts with β-catenin, YAP, and PTEN, has been recently implicated in the progression of various human malignancies, including colorectal cancer. We report here that NHERF1 acts as a tumor suppressor in vivo for intestinal adenoma development. NHERF1 is highly expressed at the apical membrane of mucosa intestinal epithelial cells (IECs) and serosa mesothelial cells. NHERF1-deficient mice show overall longer small intestine and colon that most likely could be attributed to a combination of defects, including altered apical brush border of absorbtive IECs and increased number of secretory IECs. NHERF1 deficiency in Apc(Min/+) mice resulted in significantly shorter animal survival due to markedly increased tumor burden. This resulted from a moderate increase of the overall tumor density, more pronounced in females than males, and a massive increase in the number of large adenomas in both genders. The analysis of possible pathways controlling tumor size showed upregulation of Wnt-β-catenin pathway, higher expression of unphosphorylated YAP, and prominent nuclear expression of cyclin D1 in NHERF1-deficient tumors. Similar YAP changes, with relative decrease of phosphorylated YAP and increase of nuclear YAP expression, were observed as early as the adenoma stages in the progression of human colorectal cancer. This study discusses a complex role of NHERF1 for intestinal morphology and presents indisputable evidence for its in vivo tumor suppressor function upstream of Wnt-β-catenin and Hippo-YAP pathways.
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spelling pubmed-50180972016-09-16 NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia() Georgescu, Maria-Magdalena Gagea, Mihai Cote, Gilbert Neoplasia Article NHERF1/EBP50, an adaptor molecule that interacts with β-catenin, YAP, and PTEN, has been recently implicated in the progression of various human malignancies, including colorectal cancer. We report here that NHERF1 acts as a tumor suppressor in vivo for intestinal adenoma development. NHERF1 is highly expressed at the apical membrane of mucosa intestinal epithelial cells (IECs) and serosa mesothelial cells. NHERF1-deficient mice show overall longer small intestine and colon that most likely could be attributed to a combination of defects, including altered apical brush border of absorbtive IECs and increased number of secretory IECs. NHERF1 deficiency in Apc(Min/+) mice resulted in significantly shorter animal survival due to markedly increased tumor burden. This resulted from a moderate increase of the overall tumor density, more pronounced in females than males, and a massive increase in the number of large adenomas in both genders. The analysis of possible pathways controlling tumor size showed upregulation of Wnt-β-catenin pathway, higher expression of unphosphorylated YAP, and prominent nuclear expression of cyclin D1 in NHERF1-deficient tumors. Similar YAP changes, with relative decrease of phosphorylated YAP and increase of nuclear YAP expression, were observed as early as the adenoma stages in the progression of human colorectal cancer. This study discusses a complex role of NHERF1 for intestinal morphology and presents indisputable evidence for its in vivo tumor suppressor function upstream of Wnt-β-catenin and Hippo-YAP pathways. Neoplasia Press 2016-09-09 /pmc/articles/PMC5018097/ /pubmed/27566107 http://dx.doi.org/10.1016/j.neo.2016.07.003 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Georgescu, Maria-Magdalena
Gagea, Mihai
Cote, Gilbert
NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title_full NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title_fullStr NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title_full_unstemmed NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title_short NHERF1/EBP50 Suppresses Wnt-β-Catenin Pathway–Driven Intestinal Neoplasia()
title_sort nherf1/ebp50 suppresses wnt-β-catenin pathway–driven intestinal neoplasia()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018097/
https://www.ncbi.nlm.nih.gov/pubmed/27566107
http://dx.doi.org/10.1016/j.neo.2016.07.003
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