Protein N-glycosylation in oral cancer: dysregulated cellular networks among DPAGT1, E-cadherin adhesion and canonical Wnt signaling.
Protein N-glycosylation in oral cancer: dysregulated cellular networks among DPAGT1, E-cadherin adhesion and canonical Wnt signaling.
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DOI：
10.1093/glycob/cwu031
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发表时间：
2014-07
期刊：
影响因子：
4.3
通讯作者：
Kukuruzinska MA
中科院分区：
文献类型：
--
作者：
Varelas X;Bouchie MP;Kukuruzinska MA
蛋白质的N-连接糖基化（N-糖基化）长期以来一直与肿瘤发生有关，但直到最近才开始解开这种关系的分子机制。在这里，我们回顾研究描述如何失调的N-糖基化调节基因，DPAGT 1，驱动口腔癌。DPAGT 1编码内质网中脂质连接寡糖前体组装中的第一个限速酶，因此介导许多癌症相关蛋白的N-糖基化。DPAGT 1控制E-钙粘蛋白的N-糖基化，E-钙粘蛋白是主要的上皮细胞-细胞粘附受体和肿瘤抑制因子，从而影响细胞间粘附和细胞骨架动力学。DPAGT 1还调节Wnt/β-连环蛋白信号传导并受其调节，影响稳态组织中增殖和粘附之间的平衡。因此，DPAGT 1的异常诱导促进了Wnt/β-连环蛋白的正反馈网络，其抑制基于E-钙粘蛋白的粘附并驱动肿瘤发生表型。此外，已知用N-聚糖修饰受体酪氨酸激酶（RTK）通过半乳糖凝集素晶格控制其表面呈递，因此DPAGT 1表达增加可能有助于口腔癌中RTK的异常激活。总的来说，这些研究表明，DPAGT 1/Wnt/E-cadherin网络的失调是口腔癌的病因和发病机制的基础。
N-Linked glycosylation (N-glycosylation) of proteins has long been associated with oncogenesis, but not until recently have the molecular mechanisms underlying this relationship begun to be unraveled. Here, we review studies describing how dysregulation of the N-glycosylation-regulating gene, DPAGT1, drives oral cancer. DPAGT1 encodes the first and rate-limiting enzyme in the assembly of the lipid-linked oligosaccharide precursor in the endoplasmic reticulum and thus mediates N-glycosylation of many cancer-related proteins. DPAGT1 controls N-glycosylation of E-cadherin, the major epithelial cell–cell adhesion receptor and a tumor suppressor, thereby affecting intercellular adhesion and cytoskeletal dynamics. DPAGT1 also regulates and is regulated by Wnt/β-catenin signaling, impacting the balance between proliferation and adhesion in homeostatic tissues. Thus, aberrant induction of DPAGT1 promotes a positive feedback network with Wnt/β-catenin that represses E-cadherin-based adhesion and drives tumorigenic phenotypes. Further, modification of receptor tyrosine kinases (RTKs) with N-glycans is known to control their surface presentation via the galectin lattice, and thus increased DPAGT1 expression likely contributes to abnormal activation of RTKs in oral cancer. Collectively, these studies suggest that dysregulation of the DPAGT1/Wnt/E-cadherin network underlies the etiology and pathogenesis of oral cancer.
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影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
影响因子：
64.5
作者：
Dennis JW;Nabi IR;Demetriou M
通讯作者：
Demetriou M
DOI：
10.1083/jcb.153.5.1049
发表时间：
2001-05-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Wong E;Gumbiner BM
通讯作者：
Gumbiner BM
影响因子：
2
作者：
Arroyo Carrera, Ignacio;Matthijs, Gert;Perez Cerda, Celia
通讯作者：
Perez Cerda, Celia
影响因子：
4
作者：
Bolós, V;Peinado, H;Cano, A
通讯作者：
Cano, A