OGA heterozygosity suppresses intestinal tumorigenesis in Apc(min/+) mice.

Citation data:

Oncogenesis, ISSN: 2157-9024, Vol: 3, Issue: 7, Page: e109

Publication Year:
2014
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Abstract Views 6
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Citations 8
Citation Indexes 8
Repository URL:
http://scholarworks.unist.ac.kr/handle/201301/6131
PMID:
25000257
DOI:
10.1038/oncsis.2014.24
PMCID:
PMC4150210
Author(s):
Yang, Yongryoul; Jang H.J.; Yoon, Sunyoung; Lee, Yonghwa; Nam, Dougu; Kim, I.S.; Lee, Heeseok; Kim, Hyun; Choi, Jang Hyun; Kang, Byoung Heon; Ryu, Sungho; Suh, Pann-Ghill Show More Hide
Publisher(s):
Springer Nature; Nature Publishing Group
Tags:
Biochemistry, Genetics and Molecular Biology; O-GLCNAC TRANSFERASE; BETA-N-ACETYLGLUCOSAMINE; PROSTATE-CANCER CELLS; GLCNACYLATION; METASTASIS; STABILITY; CATENIN; PHOSPHORYLATION; TRANSCRIPTION; LOCALIZATION
article description
Emerging evidence suggests that aberrant O-GlcNAcylation is associated with tumorigenesis. Many oncogenic factors are O-GlcNAcylated, which modulates their functions. However, it remains unclear how O-GlcNAcylation and O-GlcNAc cycling enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), affect the development of cancer in animal models. In this study, we show that reduced level of OGA attenuates colorectal tumorigenesis induced by Adenomatous polyposis coli (Apc) mutation. The levels of O-GlcNAcylation and O-GlcNAc cycling enzymes were simultaneously upregulated in intestinal adenomas from mice, and in human patients. In two independent microarray data sets, the expression of OGA and OGT was significantly associated with poor cancer-specific survival of colorectal cancer (CRC) patients. In addition, OGA heterozygosity, which results in increased levels of O-GlcNAcylation, attenuated intestinal tumor formation in the Apc(min/+) background. Apc(min/+) OGA(+/-) mice exhibited a significantly increased survival rate compared with Apc(min/+) mice. Consistent with this, Apc(min/+) OGA(+/-) mice expressed lower levels of Wnt target genes than Apc(min/+). However, the knockout of OGA did not affect Wnt/β-catenin signaling. Overall, these findings suggest that OGA is crucial for tumor growth in CRC independently of Wnt/β-catenin signaling.