The polypeptide N-acetylgalactosaminyltransferase 4 exhibits stage-dependent expression in colorectal cancer and affects tumorigenesis, invasion and differentiation
The polypeptide N-acetylgalactosaminyltransferase 4 exhibits stage-dependent expression in colorectal cancer and affects tumorigenesis, invasion and differentiation
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多肽N-乙酰半乳糖氨基转移酶4在结直肠癌中表现出阶段依赖性表达并影响肿瘤发生、侵袭和分化
DOI：
10.1111/febs.14593
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发表时间：
2018
期刊：
影响因子：
5.4
通讯作者：
Zhang Yan
中科院分区：
文献类型：
--
作者：
Yan Xialin;Lu Jishun;Zou Xia;Zhang Sen;Cui Yalu;Zhou Leqi;Liu Feng;Shan Aidong;Lu Jiaoyang;Zheng Minghua;Feng Bo;Zhang Yan
粘蛋白糖基化的异常表达在肿瘤的恶性发展中起着重要作用。多肽N-乙酰半乳糖胺转移酶(ppGalNAc-ts)是一类在细胞内启动粘蛋白糖基化的保守酶家族。在人类中，在癌症发生过程中ppGalNAc-ts表达的持续上调或下调已被频繁报道。在这里，我们提供的证据表明，ppGalNAc-T4在62对配对的肿瘤/正常组织中显示出在结直肠癌(CRC)不同阶段的表达。在大肠癌细胞中过表达ppGalNAc-T4可促进克隆形成和球体形成，提示ppGalNAc-T4在肿瘤发生中起重要作用。相反，在结直肠癌细胞中，ppGalNAc-T4的敲除增加了细胞的迁移和侵袭，并导致了上皮-间充质转变样的转变。进一步分析提示，ppGalNAc-T4的缺失与结直肠癌的去分化有关，ppGalNAc-T4的高表达与患者的预后良好相关。综上所述，我们的结果不仅证实了ppGalNAc-T4在结直肠癌进展过程中的分期依赖性表达，而且提示这种分期依赖性的表达可能在早期促进肿瘤的发生，在晚期促进细胞的迁移和侵袭。
The aberrant expression of mucin‐typeO‐glycosylation plays important roles in cancer malignancy. The polypeptideN‐acetylgalactosaminyltransferases (ppGalNAc‐Ts) are a family of conserved enzymes that initiate the mucin‐typeO‐glycosylation in cells. In human, consistent up‐ or down‐regulation of ppGalNAc‐Ts expression during cancer development has been frequently reported. Here, we provide evidence that ppGalNAc‐T4 shows a stage‐dependent expression at the different stages of colorectal cancer (CRC) in the 62 pair‐matched tumor/normal tissues. In detail, ppGalNAc‐T4 expression is significantly induced at stage I and II but not at stage III and IV. Overexpression of ppGalNAc‐T4 in CRC cells enhances colony formation and sphere formation suggesting an important role of ppGalNAc‐T4 in tumorigenesis. Conversely, knockdown of ppGalNAc‐T4 in CRC cells increases the cell migration and invasion, and leads to an epithelial–mesenchymal transition‐like transition. Further analysis suggests that loss of ppGalNAc‐T4 contributes to the dedifferentiation of CRC and high expression of ppGalNAc‐T4 correlates to a good prognosis of patients. Taken together, our results not only demonstrate a stage‐dependent expression of ppGalNAc‐T4 in CRC progression, but also suggest that such stage‐dependent expression may contribute to the tumorigenesis at the early stage and promote cell migration and invasion at the advanced stage.