B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma
B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma
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DOI：
10.1016/j.ajpath.2011.05.025
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发表时间：
2011-09-01
影响因子：
6
通讯作者：
Huang, Min-Chuan
中科院分区：
文献类型：
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作者：
Hsu, Wen-Ming;Che, Mei-leng;Huang, Min-Chuan
β1，4-N-乙酰半乳糖胺转移酶III(B4GALNT3)促进GalNAcβ1，4GlcNAc(LacdiNAc或LDN)的形成。果蝇β1，4-N-乙酰半乳糖胺转移酶A(B4GALNTA)参与LDN的合成，有助于调节神经元的发育。本研究探讨B4GALNT3在人神经母细胞瘤中的表达及作用。我们使用IHC分析了87个NB肿瘤，并确定了B4GALNT3的表达与包括患者生存在内的临床病理因素的相关性。研究了重组B4GALNT3对SK-N-SH和SH-SY5Y NB细胞行为和信号转导的影响。单因素和多因素分析显示，B4GALNT3在Nb肿瘤中的高表达与良好的组织学特征(P<；0.001，chi(2)检验)和早期临床分期(P=0.041，chi(2)检验)相关，是预后良好的预后因素。B4GALNT3在SK-N-SH和SH-SY5Y细胞中的重新表达抑制了细胞的增殖、集落形成、迁移和侵袭。此外，B4GALNT3增加了β(1)、整合素的LacdiNAc修饰，导致粘着斑激酶(FAK)、Src、paxlin、Akt和ERK1/2的磷酸化降低。B4GALNT3介导的细胞迁移和侵袭抑制基本上被构成活性的Akt或MEK的同时表达所逆转。我们的结论是，B4GALNT3通过减少β(1)整合素信号通路，预测了NB的良好预后，并抑制了恶性表型。(Am J Pathol2011,179：1394-1404；doi：10.1016/j.ajpath.2011.05.025)
beta 1,4-N-acetylgalactosaminyltransferase III (B4GALNT3) promotes the formation of GalNAc beta 1,4GlcNAc (LacdiNAc or LDN). Drosophila beta 1,4-N-acetylgalactosaminyltransferase A (B4GALNTA) contributes to the synthesis of LDN, which helps regulate neuronal development. In this study, we investigated the expression and role of B4GALNT3 in human neuroblastoma (NB). We used IHC analysis to examine 87 NB tumors, and we identified correlations between B4GALNT3 expression and clinicopathologic factors, including patient survival. Effects of recombinant B4GALNT3 on cell behavior and signaling were studied in SK-N-SH and SH-SY5Y NB cells. Increased expression of B4GALNT3 in NB tumors correlated with a favorable histologic profile (P < 0.001, chi(2) test) and early clinical staging (P = 0.041, chi(2) test) and was a favorable prognostic factor for survival as evaluated by univariate and multivariate analyses. Reexpression of B4GALNT3 in SK-N-SH and SH-SY5Y cells suppressed cell proliferation, colony formation, migration, and invasion. Moreover, B4GALNT3 increased the LacdiNAc modification of beta(1), integrin, leading to decreased phosphorylation of focal adhesion kinase (FAK), Src, paxillin, Akt, and ERK1/2. B4GALNT3-mediated suppression of cell migration and invasion were substantially reversed by concomitant expression of constitutively active Akt or MEK. We conclude that B4GALNT3 predicts a favorable prognosis for NB and suppresses the malignant phenotype via decreasing beta(1), integrin signaling. (Am J Pathol 2011, 179:1394-1404; DOI: 10.1016/j.ajpath.2011.05.025)