Deryugina Elena I, Quigley James P
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Biomed Biotechnol. 2012;2012:564259. doi: 10.1155/2012/564259. Epub 2012 Oct 14.
Plasmin, one of the most potent and reactive serine proteases, is involved in various physiological processes, including embryo development, thrombolysis, wound healing and cancer progression. The proteolytic activity of plasmin is tightly regulated through activation of its precursor, plasminogen, only at specific times and in defined locales as well as through inhibition of active plasmin by its abundant natural inhibitors. By exploiting the plasminogen activating system and overexpressing distinct components of the plasminogen activation cascade, such as pro-uPA, uPAR and plasminogen receptors, malignant cells can enhance the generation of plasmin which in turn, modifies the tumor microenvironment to sustain cancer progression. While plasmin-mediated degradation and modification of extracellular matrix proteins, release of growth factors and cytokines from the stroma as well as activation of several matrix metalloproteinase zymogens, all have been a focus of cancer research studies for decades, the ability of plasmin to cleave transmembrane molecules and thereby to generate functionally important cleaved products which induce outside-in signal transduction, has just begun to receive sufficient attention. Herein, we highlight this relatively understudied, but important function of the plasmin enzyme as it is generated de novo at the interface between cross-talking cancer and host cells.
纤溶酶是最具活性和反应性的丝氨酸蛋白酶之一，参与多种生理过程，包括胚胎发育、溶栓、伤口愈合和癌症进展。纤溶酶的蛋白水解活性通过其前体纤溶酶原的激活受到严格调控，仅在特定时间和特定部位进行，并且还受到其丰富的天然抑制剂对活性纤溶酶的抑制。通过利用纤溶酶原激活系统并过表达纤溶酶原激活级联反应的不同组分，如前尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体和纤溶酶原受体，恶性细胞可以增强纤溶酶的生成，进而改变肿瘤微环境以维持癌症进展。虽然几十年来，纤溶酶介导的细胞外基质蛋白降解和修饰、基质中生长因子和细胞因子的释放以及几种基质金属蛋白酶原的激活一直是癌症研究的重点，但纤溶酶切割跨膜分子从而产生诱导外向内信号转导的功能重要切割产物的能力才刚刚开始受到足够的关注。在此，我们强调纤溶酶这种相对未被充分研究但重要的功能，因为它是在相互作用的癌细胞与宿主细胞界面处重新产生的。
