Open AccessAberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
Author(s) -
Jiang Yuliang,
Liu Zhe,
Xu Feng,
Dong Xichen,
Cheng Yurong,
Hu Yizhang,
Gao Tianbo,
Liu Jian,
Yang Lei,
Jia Xingyuan,
Qian Haili,
Wen Tao,
An Guangyu
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13752
Subject(s) - carcinogenesis , glycosylation , biology , cancer research , colorectal cancer , transfection , cancer , microbiology and biotechnology , cell culture , antigen , cell growth , dna methylation , gene expression , gene , immunology , genetics
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 ( LS 174T), 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 LS 174T cells with WT Cosmc restored mature O‐glycosylation, which subsequently down‐regulated cancer cell proliferation, migration and apoptotic‐resistant ability. Significantly, the expression of MUC 2, a heavily O‐glycosylated glycoprotein that plays an essential role in intestinal function, was uniformly reduced in human CRC tissues as well as in LS 174T cells. These data suggest that aberrant O‐glycosylation contributes to the development of CRC through direct induction of oncogenic properties in cancer cells.