Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
J Pathol. 2010 Dec;222(4):367-79. doi: 10.1002/path.2776.
Nasopharyngeal carcinoma (NPC) is known for its highly metastatic character. Recent advances in diagnosis and treatment have not improved the high mortality rate that is attributable to early metastasis. Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. We demonstrate comprehensively that fibulin-3 is down-regulated in NPC. Loss of fibulin-3 expression is significantly correlated with advanced tumour and lymph node-metastasis stages, and indicates a poor 5-year survival rate. Functionally, fibulin-3 has the ability to suppress cell migration and invasion in NPC cancer cells by decreasing the activity of phospho-AKT. Conversely, its depletion by fibulin-3-mediated siRNAs may elevate phospho-AKT activity and significantly enhance the ability of NPC cancer cells to migrate and invade. Consistent with this negative association between fibulin-3 and phospho-AKT, their expression levels are inversely correlated in NPC specimens by immunohistochemical analysis. Thus, lower fibulin-3 expression is an important indicator of poor survival. It may also contribute to the development of new therapeutic strategies to block the PI3K/AKT pathway in NPC cancer cells.
鼻咽癌（NPC）以其高度转移性为特征。尽管在诊断和治疗方面取得了一些进展，但仍未能降低因早期转移而导致的高死亡率。虽然有一些生物标志物与转移和预后相关，但 NPC 发生和发展的分子机制仍不清楚。我们全面证明了纤连蛋白-3在 NPC 中下调。纤连蛋白-3 的表达缺失与肿瘤和淋巴结转移的晚期阶段显著相关，并提示 5 年生存率较差。功能上，纤连蛋白-3 通过降低磷酸化 AKT 的活性，具有抑制 NPC 癌细胞迁移和侵袭的能力。相反，纤连蛋白-3 通过 siRNA 介导的耗竭可能会增加磷酸化 AKT 的活性，并显著增强 NPC 癌细胞的迁移和侵袭能力。与纤连蛋白-3 和磷酸化 AKT 之间的这种负相关一致，免疫组织化学分析显示 NPC 标本中它们的表达水平呈负相关。因此，较低的纤连蛋白-3 表达是预后不良的一个重要指标。它也可能有助于开发新的治疗策略，以阻断 NPC 癌细胞中的 PI3K/AKT 通路。
