Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2

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

doi:10.1126/science.1069094

Cited by 832 publications

(762 citation statements)

References 15 publications

Supporting

Mentioning

701

Contrasting

Unclassified

Order By: Relevance

“…As the predominant O‐glycoprotein, MUC2 is heavily modified by O‐glycosylation and is generally considered to be essential for epithelial protection. MUC2‐lacking mice spontaneously developed colitis and colorectal cancer 53. Therefore, we assume that defective O‐glycosylation may affect the expression and/or function of MUC2 that is required for suppressing intestinal cancer.…”

Section: Discussionmentioning

confidence: 99%

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Jiang

Liu

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Aberrant O‐glycosylation is frequently observed in colorectal cancer (CRC) patients, but it is unclear if it contributes intrinsically to tumorigenesis. Here, we investigated the biological consequences of aberrant O‐glycosylation in CRC. We first detected the expression profile of Tn antigen in a serial of human CRC tissues and then explored the genetic and biosynthetic mechanisms. Moreover, we used a human CRC cell line (LS174T), which express Tn antigen, to assess whether aberrant O‐glycosylation can directly promote oncogenic properties. It showed that Tn antigen was detected in around 86% human primary and metastatic CRC tissues. Bio‐functional investigations showed that T‐synthase and Cosmc were both impaired in cancer tissues. A further analysis detected an occurrence of hypermethylation of Cosmc gene, which possibly caused its loss‐of‐function and a consequent inactive T‐synthase. Transfection of LS174T cells with WT Cosmc restored mature O‐glycosylation, which subsequently down‐regulated cancer cell proliferation, migration and apoptotic‐resistant ability. Significantly, the expression of MUC2, a heavily O‐glycosylated glycoprotein that plays an essential role in intestinal function, was uniformly reduced in human CRC tissues as well as in LS174T cells. These data suggest that aberrant O‐glycosylation contributes to the development of CRC through direct induction of oncogenic properties in cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Jiang

Liu

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Six-to eight-week-old C57BL/6 and Muc2 Ϫ/Ϫ mice, the latter originally described by Velcich et al, 13 were purchased from Charles River Laboratories International (Montreal, QC, Canada) or were bred in the animal care facilities at the University of Calgary and McMaster University. The mice were kept in sterilized, filter-topped cages, handled in tissue culture hoods, and fed autoclaved food and water under specific pathogen-free conditions.…”

Section: Animalsmentioning

confidence: 99%

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wallace

Vong

Dharmani

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Mucus is known to contribute significantly to the prevention and repair of mucosal damage throughout the gastrointestinal tract. Although not normally expressed in the stomach, mucin-2 (MUC-2, encoded by the MUC2 gene) is expressed in certain disease states. The aim of this study was to determine in a mouse model whether the absence of Muc-2 would result in impaired susceptibility to and healing of gastric mucosal injury. Acute gastric damage was induced in mice deficient in Muc-2 and in wild-type controls, through oral administration of indomethacin. Chronic gastric ulcers were induced by serosal application of acetic acid. The extent of injury and the extent of healing of the damage over time were examined in both models. Indomethacin administration caused similar levels of gastric damage in Muc-2-deficient and wild-type mice, but the erosions healed more slowly in the former. Acetic acid-induced gastric ulcers were initially similar in size in Muc-2-deficient and wildtype mice of both sexes, but ulcer healing was significantly impaired in male Muc-2-deficient mice. Induction of cyclooxygenase-2 in the stomach, in response to indomethacin-or acetic acid-induced ulceration, was significantly reduced in male Muc-2-deficient mice. This phenomenon, and the sex specificity, was also apparent in bone marrow-derived macrophages stimulated with endotoxin. These results demonstrate a marked impairment of gastric mucosal repair in male Muc-2-deficient mice that may be related to an insufficient induction of cyclooxygenase-2, an enzyme known to contribute to mucosal repair.

show abstract

“…Homozygous mutation in the Muc2 gene that encodes the most abundant secreted gastrointestinal (GI) mucin causes adenomas and adenocarcinomas in the intestines (Velcich et al, 2002). Although the incidence and multiplicity are low, the adenocarcinoma is locally invasive without distant metastasis.…”

Section: Mouse Models For Colon Cancermentioning

confidence: 99%

Wnt signaling and gastrointestinal tumorigenesis in mouse models

Taketo

2006

Oncogene

View full text Add to dashboard Cite

The canonical Wnt signaling plays important roles in embryonic development and tumorigenesis. For the latter, induced mutations in mice have greatly contributed to our understanding of the molecular mechanisms of cancer initiation and progression. Here, I will review recent reports on gastrointestinal cancer model mice, with an emphasis on the roles of the Wnt signal pathway. They include: mouse models for familial adenomatous polyposis; modifying factors that affect mouse intestinal polyposis, including the genes that help cancer progression; Wnt target genes that affect mouse intestinal polyposis; and a mouse model of gastric cancer that mimics Helicobacter pyroli infection.

show abstract

Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2

Cited by 832 publications

References 15 publications

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

Wnt signaling and gastrointestinal tumorigenesis in mouse models

Contact Info

Product

Resources

About