An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1

An induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/β-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2...

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Main Authors: Arka Saha, Nancy Gavert, Thomas Brabletz, Avri Ben-Ze’ev
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/17/13418
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author Arka Saha
Nancy Gavert
Thomas Brabletz
Avri Ben-Ze’ev
author_facet Arka Saha
Nancy Gavert
Thomas Brabletz
Avri Ben-Ze’ev
author_sort Arka Saha
collection DOAJ
description An induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/β-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2 among the most abundant secreted proteins. We found that suppressing Mucin2 expression in L1-expressing colon cancer cells inhibits cell proliferation, motility, tumorigenesis, and liver metastasis. We detected several signaling pathways involved in Mucin2 induction in L1-expressing cells. In human colon cancer tissue, Mucin2 expression was significantly reduced or lost in the adenocarcinoma tissue, while in the mucinous subtype of colon cancer tissue, Mucin2 expression was increased. An increased signature of <i>L1</i>/<i>Mucin2</i> expression reduced the survival rate of human colon cancer patients. Thus, induction of Mucin2 expression by L1 is required during mucinous colon cancer progression and can serve as a marker for diagnosis and a target for therapy<b>.</b>
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spelling doaj.art-0c1d3c28290b4dcaa771884f61c658822023-11-19T08:17:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171341810.3390/ijms241713418An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1Arka Saha0Nancy Gavert1Thomas Brabletz2Avri Ben-Ze’ev3Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Experimental Medicine I, Nikolaus-Feibiger-Center for Molecular Medicine, University of Erlangen-Nuernberg, 91054 Erlangen, GermanyDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelAn induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/β-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2 among the most abundant secreted proteins. We found that suppressing Mucin2 expression in L1-expressing colon cancer cells inhibits cell proliferation, motility, tumorigenesis, and liver metastasis. We detected several signaling pathways involved in Mucin2 induction in L1-expressing cells. In human colon cancer tissue, Mucin2 expression was significantly reduced or lost in the adenocarcinoma tissue, while in the mucinous subtype of colon cancer tissue, Mucin2 expression was increased. An increased signature of <i>L1</i>/<i>Mucin2</i> expression reduced the survival rate of human colon cancer patients. Thus, induction of Mucin2 expression by L1 is required during mucinous colon cancer progression and can serve as a marker for diagnosis and a target for therapy<b>.</b>https://www.mdpi.com/1422-0067/24/17/13418Mucin2L1colon cancertumorigenesismetastasis
spellingShingle Arka Saha
Nancy Gavert
Thomas Brabletz
Avri Ben-Ze’ev
An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
International Journal of Molecular Sciences
Mucin2
L1
colon cancer
tumorigenesis
metastasis
title An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
title_full An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
title_fullStr An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
title_full_unstemmed An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
title_short An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1
title_sort increase in mucin2 expression is required for colon cancer progression mediated by l1
topic Mucin2
L1
colon cancer
tumorigenesis
metastasis
url https://www.mdpi.com/1422-0067/24/17/13418
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