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J Cell Mol Med. 2018 Oct;22(10):4875-4885. doi: 10.1111/jcmm.13752. Epub 2018 Jul 12.

Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer.

Author information

1
Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
2
Medical research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
3
Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Abstract

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.

KEYWORDS:

Colorectal cancer; MUC2; O-glycosylation; Tn antigen; mucin

PMID:
29999571
PMCID:
PMC6156240
DOI:
10.1111/jcmm.13752
[Indexed for MEDLINE]
Free PMC Article

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