Quantitative glycoproteomics analysis reveals changes in N-glycosylation level associated with pancreatic ductal adenocarcinoma.
Quantitative glycoproteomics analysis reveals changes in N-glycosylation level associated with pancreatic ductal adenocarcinoma.
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DOI：
10.1021/pr4010184
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发表时间：
2014-03-07
影响因子：
4.4
通讯作者：
Brentnall, Teresa A.
中科院分区：
文献类型：
--
作者：
Pan, Sheng;Chen, Ru;Tamura, Yasuko;Crispin, David A.;Lai, Lisa A.;May, Damon H.;McIntosh, Martin W.;Goodlett, David R.;Brentnall, Teresa A.
关键词：
糖基化在包括胰腺导管腺癌在内的上皮性癌症中起重要作用。然而，关于人类胰腺的糖蛋白组及其与胰腺肿瘤发生相关的改变知之甚少。采用定量糖蛋白组学方法，我们研究了胰腺肿瘤组织中蛋白n -糖基化与正常胰腺和慢性胰腺炎组织的比较。该研究发现了一系列与胰腺癌相关的n-糖基化水平异常的糖蛋白，包括粘蛋白- 5ac （MUC5AC）、癌胚抗原相关细胞粘附分子5 （CEACAM5）、胰岛素样生长因子结合蛋白（IGFBP3）和半乳糖凝集素-3结合蛋白（LGALS3BP）。对癌症相关异常糖蛋白的通路分析揭示了一个新现象，即n -糖基化活性的增加与几种胰腺癌通路有关，包括TGF-β、TNF、NF-kappa-B和tfeb相关的溶酶体改变。此外，该研究提供的证据表明，某些单个蛋白质中的特定n -糖基化位点可以显著改变胰腺癌中糖基化的占用，这反映了癌症相关糖基化事件的分子机制的复杂性。
Glycosylation plays an important role in epithelial cancers, including pancreatic ductal adenocarcinoma. However, little is known about the glycoproteome of the human pancreas or its alterations associated with pancreatic tumorigenesis. Using quantitative glycoproteomics approach, we investigated protein N-glycosylation in pancreatic tumor tissue in comparison with normal pancreas and chronic pancreatitis tissue. The study lead to the discovery of a roster of glycoproteins with aberrant N-glycosylation level associated with pancreatic cancer, including mucin-5AC (MUC5AC), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), insulin-like growth factor binding protein (IGFBP3), and galectin-3-binding protein (LGALS3BP). Pathway analysis of cancer-associated aberrant glycoproteins revealed an emerging phenomenon that increased activity of N-glycosylation was implicated in several pancreatic cancer pathways, including TGF-β, TNF, NF-kappa-B, and TFEB-related lysosomal changes. In addition, the study provided evidence that specific N-glycosylation sites within certain individual proteins can have significantly altered glycosylation occupancy in pancreatic cancer, reflecting the complexity of the molecular mechanisms underlying cancer-associated glycosylation events.
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影响因子：
3.7
作者：
Maupin KA;Sinha A;Eugster E;Miller J;Ross J;Paulino V;Keshamouni VG;Tran N;Berens M;Webb C;Haab BB
通讯作者：
Haab BB
影响因子：
3.7
作者：
Brentnall TA;Lai LA;Coleman J;Bronner MP;Pan S;Chen R
通讯作者：
Chen R
影响因子：
14.5
作者：
Lapis, K;Tímár, J
通讯作者：
Tímár, J
影响因子：
4
作者：
Kobata, A;Amano, J
通讯作者：
Amano, J
影响因子：
6.4
作者：
Okuyama, N;Ide, Y;Miyoshi, E
通讯作者：
Miyoshi, E