期刊
BIOCHEMICAL JOURNAL
卷 407, 期 -, 页码 153-159出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20071037
关键词
integrin; oral squamous cell carcinoma (OSCC); proteinase; proteolysis; urinary-type plasminogen activator (uPA); uPA receptor (uPAR)
资金
- NCI NIH HHS [R01 CA85870] Funding Source: Medline
OSCC (oral squamous cell carcinoma) is the most common oral malignancy and is estimated to affect approx. 350 000 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.
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