Department of Pathology, the First Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
PLoS One. 2013;8(4):e60821. doi: 10.1371/journal.pone.0060821. Epub 2013 Apr 3.
The present study was aimed at investigating the expression of metastasis-associated in colon cancer 1 (MACC1) in nasopharyngeal carcinoma (NPC), its relationship with β-catenin, Met expression and the clinicopathological features of NPC, and its roles in carcinogenesis of NPC. Our results showed that MACC1 expression was higher in NPC cells and tissues than that in normal nasopharyngeal cells and chronic inflammation of the nasopharynx tissues, respectively. MACC1 expression was closely related to the clinical stage (p = 0.005) and the N classification (p<0.05) of NPC. Significant correlations between MACC1 expression and Met expression (p = 0.003), MACC1 expression and β-catenin abnormal expression (p = 0.033) were found in NPC tissues. MACC1 knockdown dramatically inhibited cellular proliferation, migration, invasion, and colony formation, but induced apoptosis in NPC cells compared with the control group. Furthermore, MACC1 down-regulation inhibited phosphorylated-Akt (Ser473) and β-catenin expression in NPC cells, but phosphorylated-Erk1/2 expression was not altered. Further study showed that phosphotidylinsitol-3-kinase inhibitor downregulated β-catenin and Met expression in NPC cells. There was a significant relationship between MACC1 expression and phosphorylated-Akt expression (p = 0.03), β-catenin abnormal expression and phosphorylated-Akt expression (p = 0.012) in NPC tissue, respectively. In addition, Epstein Barr virus-encoded oncogene latent membrane protein 1 upregulated MACC1 expression in NPC cells. Our results firstly suggest that MACC1 plays an important role in carcinogenesis of NPC through Akt/β-catenin signaling pathway. Targeting MACC1 may be a novel therapeutic strategy for NPC.
本研究旨在探讨结肠癌转移相关基因 1（MACC1）在鼻咽癌（NPC）中的表达及其与β-连环蛋白、Met 表达及 NPC 临床病理特征的关系，并探讨其在 NPC 发生发展中的作用。我们的结果显示，MACC1 在 NPC 细胞和组织中的表达高于正常鼻咽细胞和慢性鼻咽炎症组织。MACC1 的表达与 NPC 的临床分期（p=0.005）和 N 分类（p<0.05）密切相关。在 NPC 组织中，MACC1 表达与 Met 表达（p=0.003）和 MACC1 表达与β-连环蛋白异常表达（p=0.033）均存在显著相关性。与对照组相比，MACC1 敲低显著抑制 NPC 细胞的增殖、迁移、侵袭和集落形成，但诱导 NPC 细胞凋亡。此外，MACC1 下调抑制 NPC 细胞中磷酸化-Akt（Ser473）和β-连环蛋白的表达，但磷酸化-Erk1/2 的表达没有改变。进一步的研究表明，磷酸肌醇-3-激酶抑制剂下调 NPC 细胞中β-连环蛋白和 Met 的表达。在 NPC 组织中，MACC1 表达与磷酸化-Akt 表达之间存在显著的相关性（p=0.03），β-连环蛋白异常表达与磷酸化-Akt 表达之间存在显著的相关性（p=0.012）。此外，Epstein Barr 病毒编码的癌基因潜伏膜蛋白 1上调 NPC 细胞中 MACC1 的表达。我们的研究结果首次表明，MACC1 通过 Akt/β-连环蛋白信号通路在 NPC 的发生发展中发挥重要作用。靶向 MACC1 可能是 NPC 的一种新的治疗策略。
