Cysteine Cathepsins and the cutting edge of cancer invasion

被引:343
作者
Gocheva, Vasilena
Joyce, Johanna A.
机构
[1] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA
[2] Cornell Univ, Weill Grad Sch Med Sci, New York, NY USA
关键词
cancer; cathepsin; invasion; mouse model; tumor microenvironment;
D O I
10.4161/cc.6.1.3669
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cysteine cathepsins are a family of lysosomal proteases that are often upregulated in various human cancers, and have been implicated in distinct tumorigenic processes such as angiogenesis, proliferation, apoptosis and invasion. During cancer progression, cathepsins are often translocated to the cell surface of tumor cells or are secreted into the extracellular milieu, where they can promote tumor invasion through several possible mechanisms. First, they can directly cleave components of the extracellular matrix and basement membrane, essentially clearing a path for the migration of tumor cells away from the primary tumor mass. Second, at the cell membrane, cathepsins can direct a proteolytic cascade in which they activate other proteases such as matrix metalloproteinases and urokinase plasminogen activator, which in turn promote invasion. Finally, cleavage of the cell adhesion protein, E-cadherin, at the cell surface can disrupt adherens junctions and thus facilitate cancer cell migration and invasion. Therefore, cathepsins are now emerging as major players in tumor progression, making them potential drug targets for a wide range of human cancers.
引用
收藏
页码:60 / 64
页数:5
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