期刊
JOURNAL OF PROTEOME RESEARCH
卷 7, 期 11, 页码 4792-4806出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr800357h
关键词
UPAR; two-dimensional gel electrophoresis; mass spectrometry; protein expression; colon cancer; metastasis; STMN1
Dysregulation of the plasminogen activation cascade is a prototypic feature in many malignant epithelial cancers. Principally, this is thought to occur through activation of overexpressed urokinase plasminogen activator WPM concomitant with binding to its high specificity cell surface receptor urokinase plasminogen activator receptor (uPAR). Up-regulation of uPA and uPAR in cancer appears to potentiate the malignant phenotype, either (i) directly by triggering plasm in-mediated degradation or activation of uPA's or plasmin's proteolytic targets (e.g., extracellular matrix zymogen proteases or nascent growth factors) or indirectly by simultaneously altering a range of downstream functions including signal transduction pathways (Romer, J.; Nielsen, B. S.; Ploug, M. The urokinase receptor as a potential target in cancer therapy Curr, Pharm. Des. 2004, 10 (19), 235976). Because many malignant epithelial cancers express high levels of uPAR, uPA or other components of the plasminogen activation cascade and because these are often associated with poor prognosis, characterizing how uPAR changes the downstream cellular proteome is fundamental to understanding any role in cancer. This study describes a carefully designed proteomic study of the effects of antisense uPAR suppression in a previously studied colon cancer cell line (HCT116). The study utilized replicate 2DE gels and two independent gel image analysis software packages to confidently identify 64 proteins whose expression levels changed (by :2 fold) coincident with a moderate (similar to 40%) suppression of cell-surface uPAR. Not surprisingly, many of the altered proteins have previously been implicated in the regulation of tumor progression (e.g., p53tumorsuppressor protein and c-myc oncogene protein among many others). In addition, through a combination of proteomics and immunological methods, this study demonstrates that stathmin la, a cytoskeletal protein implicated in tumor progression, undergoes a basic isoelectric point shift (p following uPAR suppression, suggesting that post-translational modification of stathmin occur secondary to uPAR suppression. Overall, these results shed new light on the molecular mechanisms involved in uPAR signaling and how it may promulgate the malignant phenotype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据