Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2

Velcich, Anna; Yang, WanCai; Heyer, Joerg; Fragale, Alessandra; Nicholas, Courtney; Viani, Stephanie; Kucherlapati, Raju; Lipkin, Martin; Yang, Kan; Augenlicht, Leonard

doi:10.1126/science.1069094

Cited by 936Glycosylation and Glycoproteins ResearchDigestive system and related healthGenetic factors in colorectal cancer

Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2

Velcich, Anna, Yang, WanCai, Heyer, Joerg, Fragale, Alessandra, Nicholas, Courtney, Viani, Stephanie, Kucherlapati, Raju, Lipkin, Martin +2 more·2002·Science

DOI 10.1126/science.1069094

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Abstract

The gastrointestinal tract is lined by a layer of mucus comprised of highly glycosylated proteins called mucins. To evaluate the importance of mucin in intestinal carcinogenesis, we constructed mice genetically deficient in Muc2, the most abundant secreted gastrointestinal mucin. Muc2 −/− mice displayed aberrant intestinal crypt morphology and altered cell maturation and migration. Most notably, the mice frequently developed adenomas in the small intestine that progressed to invasive adenocarcinoma, as well as rectal tumors. Thus, Muc2 is involved in the suppression of colorectal cancer.

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Decreased Muc2 expression has been implicated in the etiopathogenesis of sporadic and IBD-associated colon cancers.
“Additionally, decreased Muc2 expression has been implicated in the etiopathogenesis of sporadic and IBD-associated colon cancers.14,15”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [14]
Mice lacking the Muc2 gene develop spontaneous and experimentally-induced colitis.
“The importance of Muc2 in protecting the integrity of the gut epithelium is exemplified by the development of spontaneous and experimentally-induced colitis in mice lacking the Muc2 gene (Muc2-KO).14”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [14]
Other studies report down-regulation of mucin expression.
“while others report a down-regulation of their expression.14”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [14]

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Authors: Velcich, A., Yang, W., Heyer, J., Fragale, A., Nicholas, C., Viani, S., Kucherlapati, R., Lipkin, M., Yang, K., & Augenlicht, L.
Affiliations: Albert Einstein College of Medicine (US)
Yeshiva University (US)
Brigham and Women's Hospital (US)
Corresponding author: Velcich, Anna
ORCID: Yang, WanCai
Fragale, Alessandra
Nicholas, Courtney
Kucherlapati, Raju
Yang, Kan
Augenlicht, Leonard
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2002-03
Volume: 295
Issue: 5560
Pages: 1726-1729
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1069094
OpenAlex: W2018620221
Cited by: 936
References: 20
Citations by year: 2026: 21 · 2025: 29 · 2024: 36 · 2023: 41 · 2022: 47 · 2021: 52 · 2020: 52 · 2019: 41 · 2018: 49 · 2017: 51 · 2016: 42 · 2015: 37 · 2014: 55 · 2013: 52 · 2012: 38
FWCI: 10.46
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca072835-03, 5r01ca090808-05)
National Cancer Institute (CA90808, P0 CA 13330, CA 72835, P30CA013330)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: MUC2, mucin, colorectal cancer, intestinal carcinogenesis, cell migration, rectal tumors, tumor suppression, mucus
MeSH terms: Adenocarcinoma, Adenoma, Animals, Cell Differentiation, Cell Division, Cell Movement, Colon, Cytoskeletal Proteins, Duodenal Neoplasms, Duodenum, Epithelial Cells, Female, Intestinal Mucosa, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Mucins, Colorectal Neoplasms, Trans-Activators, Proto-Oncogene Proteins c-myc, Apoptosis, Gene Targeting, Disease Progression, Cell Lineage, Goblet Cells, beta Catenin, Mice, Mucin-2

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Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2

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