Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Trends Cell Biol. 2011 Apr;21(4):228-37. doi: 10.1016/j.tcb.2010.12.002. Epub 2011 Jan 12.
Proteases are important for multiple processes during malignant progression, including tumor angiogenesis, invasion and metastasis. Recent evidence reveals that tumor-promoting proteases function as part of an extensive multidirectional network of proteolytic interactions, in contrast to the unidirectional caspase cascade. These networks involve different constituents of the tumor microenvironment and key proteases, such as cathepsin B, urokinase-type plasminogen activator and several matrix metalloproteinases, occupy central nodes for amplifying proteolytic signals passing through the network. The proteolytic network interacts with other important signaling pathways in tumor biology, involving chemokines, cytokines, and kinases. Viewing these proteolytic interactions as a system of activating and inhibiting reactions provides insight into tumor biology and reveals relevant pharmaceutical targets. This review examines recent advances in understanding proteases in cancer and summarizes how the network of activity is co-opted to promote tumor progression.
蛋白酶在恶性进展过程中的多个过程中很重要，包括肿瘤血管生成、侵袭和转移。最近的证据表明，促进肿瘤的蛋白酶作为广泛的多向蛋白水解相互作用网络的一部分发挥作用，与单向胱天蛋白酶级联反应相反。这些网络涉及肿瘤微环境的不同成分和关键蛋白酶，如组织蛋白酶 B、尿激酶型纤溶酶原激活物和几种基质金属蛋白酶，占据放大通过网络传递的蛋白水解信号的中心节点。蛋白水解网络与肿瘤生物学中其他重要的信号通路相互作用，涉及趋化因子、细胞因子和激酶。将这些蛋白水解相互作用视为激活和抑制反应的系统，为深入了解肿瘤生物学提供了线索，并揭示了相关的药物靶点。本文综述了近年来对癌症中蛋白酶的理解进展，并总结了活性网络如何被篡夺以促进肿瘤进展。
