Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer.
Aberrant O-glycosylation contributes to tumorigenesis in human colorectal cancer.
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异常的O-糖基化有助于人类结直肠癌的肿瘤发生。
DOI：
10.1111/jcmm.13752
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
An G
中科院分区：
文献类型：
--
作者：
Jiang Y;Liu Z;Xu F;Dong X;Cheng Y;Hu Y;Gao T;Liu J;Yang L;Jia X;Qian H;Wen T;An G
异常O -糖基化在结直肠癌（CRC）患者中经常观察到，但目前尚不清楚它是否与肿瘤发生有关。在这里，我们研究了异常O糖基化在结直肠癌中的生物学后果。我们首先检测了Tn抗原在一系列人类结直肠癌组织中的表达谱，然后探讨了其遗传和生物合成机制。此外，我们使用表达Tn抗原的人CRC细胞系（LS174T）来评估异常O -糖基化是否可以直接促进致癌特性。结果表明，约86%的人原发性和转移性结直肠癌组织中检测到Tn抗原。生物功能研究表明，T合酶和Cosmc在肿瘤组织中均受损。进一步的分析发现Cosmc基因发生了高甲基化，这可能导致其功能丧失和随之而来的T合酶失活。转染WT Cosmc的LS174T细胞恢复了成熟的O -糖基化，从而降低了癌细胞的增殖、迁移和抗凋亡能力。值得注意的是，MUC2的表达在人CRC组织和LS174T细胞中一致降低。MUC2是一种高度O糖基化的糖蛋白，在肠功能中起重要作用。这些数据表明，异常的O -糖基化通过直接诱导癌细胞的致癌特性而促进结直肠癌的发展。
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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影响因子：
6.7
作者：
Bergstrom KS;Kissoon-Singh V;Gibson DL;Ma C;Montero M;Sham HP;Ryz N;Huang T;Velcich A;Finlay BB;Chadee K;Vallance BA
通讯作者：
Vallance BA
肠道O-聚糖的损失会促进自发性十二指肠肿瘤。
DOI：
10.1152/ajpgi.00060.2016
发表时间：
2016-07-01
影响因子：
4.5
作者：
Gao, Nan;Bergstrom, Kirk;Xia, Lijun
通讯作者：
Xia, Lijun
影响因子：
3.3
作者：
Ghazizadeh, M;Ogawa, H;Aihara, K
通讯作者：
Aihara, K
影响因子：
4
作者：
Konno, A;Hoshino, Y;Kawaguchi, T
通讯作者：
Kawaguchi, T
影响因子：
11.2
作者：
Ju, Tongzhong;Lanneau, Grainger S.;Cummings, Richard D.
通讯作者：
Cummings, Richard D.