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Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

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 s...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156240/
https://www.ncbi.nlm.nih.gov/pubmed/29999571
http://dx.doi.org/10.1111/jcmm.13752
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author 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
author_facet 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
author_sort Jiang, Yuliang
collection PubMed
description 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.
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spelling pubmed-61562402018-10-01 Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer 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 J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2018-07-12 2018-10 /pmc/articles/PMC6156240/ /pubmed/29999571 http://dx.doi.org/10.1111/jcmm.13752 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title_full Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title_fullStr Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title_full_unstemmed Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title_short Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer
title_sort aberrant o‐glycosylation contributes to tumorigenesis in human colorectal cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156240/
https://www.ncbi.nlm.nih.gov/pubmed/29999571
http://dx.doi.org/10.1111/jcmm.13752
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