Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer

Journal of Cellular and Molecular Medicine
Yuliang JiangGuangyu An

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 ...Continue Reading

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Citations

Oct 22, 2019·Journal of Cellular and Molecular Medicine·Tianbo GaoTao Wen
Dec 3, 2020·International Journal of Molecular Sciences·Takuro MatsumotoKoji Kono
Mar 2, 2021·World Journal of Gastrointestinal Surgery·Yao Liu, Fang-Xing Peng
Jun 18, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Rohit Gundamaraju, Wai Chin Chong
Dec 7, 2021·The International Journal of Biological Markers·Yongli SituZheng Shao

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Methods Mentioned

BETA
exome sequencing
PCR
transfection
FACS

Software Mentioned

GraphPad Prism
EpiDesigner
Cosmc
SEQUENOM
BWA
EpiTYPE
SPSS
inForm

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