Du Jiang, Zhang Xiupeng, Zhou Haijing, Miao Yuan, Han Yong, Han Qiang, Wang Enhua
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Tumour Biol. 2017 Jul;39(7):1010428317701441. doi: 10.1177/1010428317701441.
Alex3, is a newly identified mitochondrial protein, regulates mitochondrial dynamics and is involved in neural development. However, its expression pattern and clinicopathological relevance in human tumors are still unclear. In this study, Immunohistochemistry assay was performed in 109 cases of lung cancer samples and found that Alex 3 expression in lung cancer tissues was significantly lower than adjacent normal lung tissues (28.4% vs 52.6%, p < 0.001). Sequent statistical analysis indicated that negative Alex3 expression was significantly associated with advanced tumor-node-metastasis stages (p = 0.001), positive lymph node metastasis (p = 0.005), and poor prognosis (p = 0.008). After overexpression of Alex3, levels of p-AKT and Slug were downregulated, while level of E-cadherin was upregulated, which results in the inhibition of invasion and migration ability of lung cancer cells. In conclusion, reduction of Alex3 correlates with the development of non-small cell lung cancer and predicts adverse clinical outcome of non-small cell lung cancer patients. The effect of Alex3 on inhibiting invasion and migration may attribute to upregulation of E-cadherin expression through AKT-Slug pathway inactivation.
Alex3是一种新发现的线粒体蛋白，可调节线粒体动力学并参与神经发育。然而，其在人类肿瘤中的表达模式及临床病理相关性仍不清楚。在本研究中，对109例肺癌样本进行免疫组织化学检测，发现Alex 3在肺癌组织中的表达明显低于邻近正常肺组织（28.4%对52.6%，p < 0.001）。后续统计分析表明，Alex3阴性表达与肿瘤-淋巴结-转移晚期（p = 0.001）、阳性淋巴结转移（p = 0.005）及预后不良（p = 0.008）显著相关。Alex3过表达后，p-AKT和Slug水平下调，而E-钙黏蛋白水平上调，导致肺癌细胞侵袭和迁移能力受到抑制。总之，Alex3表达降低与非小细胞肺癌的发生发展相关，并可预测非小细胞肺癌患者的不良临床结局。Alex3对侵袭和迁移的抑制作用可能归因于通过AKT-Slug途径失活上调E-钙黏蛋白表达。
