Shi Zonggao, Stack M Sharon
Department of Pathology and Anatomical Sciences, M214E Medical Sciences Building, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.
Biochem J. 2007 Oct 15;407(2):153-9. doi: 10.1042/BJ20071037.
OSCC (oral squamous cell carcinoma) is the most common oral malignancy and is estimated to affect approx. 350000 new patients worldwide this year. OSCC is characterized by a high degree of morbidity and mortality, as most patients exhibit local, regional and distant metastasis at the time of diagnosis. Recent genome-wide screening efforts have identified the serine proteinase uPA (urinary-type plasminogen activator, also known as urokinase) as a strong biomarker for prediction of poor disease outcome and a key candidate for molecular classification of oral neoplasms using a 'gene signature' approach. The proteinase uPA binds a surface-anchored receptor designated uPAR (uPA receptor), focalizing proteolytic activity to the pericellular milieu. Furthermore, uPA-uPAR can interact with transmembrane proteins to modify multiple signal transduction pathways and influence a wide variety of cellular behaviours. Correlative clinical data show elevated uPA-uPAR in oral tumour tissues, with tumours exhibiting high levels of both uPA and uPAR as the most invasive. Combined in vitro, pre-clinical and clinical data support the need for further analysis of uPA-uPAR as a prognostic indicator as well as a potential therapeutic target in OSCC.
口腔鳞状细胞癌（OSCC）是最常见的口腔恶性肿瘤，据估计今年全球约有350000名新患者受其影响。OSCC的特点是发病率和死亡率很高，因为大多数患者在诊断时就已出现局部、区域和远处转移。最近的全基因组筛查工作已确定丝氨酸蛋白酶尿激酶型纤溶酶原激活剂（uPA，也称为尿激酶）是预测疾病不良预后的有力生物标志物，也是使用“基因特征”方法对口腔肿瘤进行分子分类的关键候选物。蛋白酶uPA与一种名为uPAR（uPA受体）的表面锚定受体结合，将蛋白水解活性集中到细胞周围环境中。此外，uPA-uPAR可与跨膜蛋白相互作用，以改变多种信号转导途径并影响多种细胞行为。相关临床数据显示，口腔肿瘤组织中uPA-uPAR水平升高，同时表达高水平uPA和uPAR的肿瘤侵袭性最强。综合体外、临床前和临床数据表明，有必要进一步分析uPA-uPAR作为OSCC预后指标以及潜在治疗靶点的作用。
