Aurora-A modulates MMP-2 expression via AKT/NF-κB pathway in esophageal squamous cell carcinoma cells
Aurora-A modulates MMP-2 expression via AKT/NF-κB pathway in esophageal squamous cell carcinoma cells
复制标题
DOI：
10.1093/abbs/gmw030
复制
发表时间：
2016-06-01
影响因子：
3.7
通讯作者：
Wang, Binquan
中科院分区：
文献类型：
--
作者：
Wang, Xiaoxia;Li, Xiaozhong;Wang, Binquan
食管鳞状细胞癌(ESCC)是最常见的恶性肿瘤之一。有必要寻找新的标记物来预测肿瘤进展和治疗分子靶点。已有研究表明，Aurora-A和基质金属蛋白酶2(MMP2)的过度表达可能促进肿瘤的恶性发展。然而，在肿瘤患者中Aurora-A和MMP2的表达之间的关系还没有被研究。此外，Aurora-A调节基质金属蛋白酶-2表达的潜在机制仍未完全阐明。在这项研究中，我们证明了极光-A和基质金属蛋白酶-2在食管鳞癌组织中的表达高于配对的正常癌旁组织(P<；0.0001)。Aurora-A的过度表达与食管癌的淋巴结转移有关(P=0.01)。食管癌组织中Aurora-A蛋白表达与基质金属蛋白酶-2蛋白表达呈正相关(r=0.0001.66，P<0.0 5)。Aurora-A的表达水平与ESCC细胞的侵袭能力呈正相关。此外，Aurora-A过表达通过上调基质金属蛋白酶-2的表达显著增加食管癌细胞的侵袭力。此外，Aurora-A过表达可促进核因子-kappaB(NF-kappaB)的激活，而Aurora-A介导的MMP-2上调可被核因子-kappaB抑制剂抑制。进一步分析表明，在过表达Aurora-A的细胞中，AKT抑制剂严重减弱了核因子-kappaB的激活。综上所述，这些数据表明，Aurora-A的过表达通过激活AKT/NF-kappa B信号通路上调了ESCC细胞中MMP2的表达。这些发现表明，Aurora-A可作为判断ESCC恶性行为的重要指标，并可能成为肿瘤治疗的一个有吸引力的靶点。
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. It is necessary to identify new markers for predicting tumor progression and therapeutic molecular targets. It has been reported that overexpressions of Aurora-A and matrix metalloproteinases 2 (MMP-2) may promote the malignant development of tumor. However, the relationship between Aurora-A and MMP-2 expression in tumor patients has not been investigated. In addition, the underlying mechanisms that Aurora-A regulates MMP-2 expression are still not fully elucidated. In this study, we demonstrated that Aurora-A and MMP-2 were overexpressed in ESCC tissues compared with paired normal adjacent tissues (P < 0.0001). Overexpression of Aurora-A was associated with the lymph node metastasis of ESCC (P = 0.01). Significantly, Aurora-A protein expression was positively correlated with MMP-2 protein expression in ESCC tissues (r = 0.66, P < 0.0001) as well as in ESCC cell lines. The level of Aurora-A expression was also positively correlated with the invasion capability of ESCC cells. Furthermore, Aurora-A overexpression significantly increased ESCC cell invasion by the upregulation of MMP-2 expression. In addition, Aurora-A overexpression promoted nuclear factor-kappaB (NF-kappa B) activation, and Aurora-A-mediated MMP-2 upregulation was abrogated by NF-kappa B inhibitor. Further analysis showed that activation of NF-kappa B was severely attenuated by AKT inhibitor in cells overexpressing Aurora-A. Taken together, these data indicate that Aurora-A overexpression upregulates MMP-2 expression through activating AKT/NF-kappa B signaling pathway in ESCC cells. These findings reveal that Aurora-A may be used as an important indicator for the judgment of malignant behavior of ESCC, and may be an attractive target for cancer therapy.