I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling.
I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling.
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DOI：
10.1111/cas.12859
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发表时间：
2016-03
期刊：
影响因子：
5.7
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Mikami J;Tobisawa Y;Yoneyama T;Hatakeyama S;Mori K;Hashimoto Y;Koie T;Ohyama C;Fukuda M
细胞表面碳水化合物对前列腺癌(Pca)的细胞迁移和侵袭具有重要作用。相应地，I-分支N-乙酰氨基葡萄糖转移酶(GCNT2)将线性I-抗原转化为I-分支糖链，其表达与乳腺癌的进展有关。在本研究中，我们确定了前列腺癌患者GCNT2表达与临床病理参数之间的关系。石蜡包埋的PCa标本用免疫组织化学方法检测GCNT2的表达，并利用高GCNT2表达和低GCNT2表达的细胞系研究GCNT2在PCa进展中的作用。在器官受限疾病中，GCNT2阳性细胞明显少于包膜外肿瘤，与GCNT2阳性肿瘤相比，GCNT2阴性肿瘤的前列腺特异性无抗原存活率显著提高。随后的功能研究表明，GCNT2在PCa细胞系中的表达下调显著地抑制了细胞的迁移和侵袭。GCNT2调节O-糖链和糖脂上细胞表面I抗原的表达。此外，携带I抗原的糖脂被α5β1整合素-纤维连接蛋白介导的蛋白激酶B磷酸化。综上所述，GCNT2的表达与PCa的侵袭潜能密切相关。
Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I‐branching N‐acetylglucosaminyltransferase (GCNT2) converts linear i‐antigen to I‐branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin‐embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2‐positive cells were significantly lesser in organ‐confined disease than in that with extra‐capsular extensions, and GCNT2‐negative tumors were associated with significantly better prostate‐specific antigen‐free survival compared with GCNT2‐positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I‐antigen on the O‐glycan and glycolipid. Moreover, I‐antigen‐bearing glycolipids were subject to α5β1 integrin–fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.