The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells

被引:292
作者
Seals, DF [1 ]
Azucena, EF [1 ]
Pass, I [1 ]
Tesfay, L [1 ]
Gordon, R [1 ]
Woodrow, M [1 ]
Resau, JH [1 ]
Courtneidge, SA [1 ]
机构
[1] Van Andel Res Inst, Grand Rapids, MI 49503 USA
关键词
D O I
10.1016/j.ccr.2005.01.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tks5/Fish is a scaffolding protein with five SH3 domains and one PX domain. In Src-transformed cells, Tks5/Fish localizes to podosomes, discrete protrusions of the ventral membrane. We generated Src-transformed cells with reduced Tks5/Fish levels. They no longer formed podosomes, did not degrade gelatin, and were poorly invasive. We detected Tks5/Fish expression in podosomes in invasive cancer cells, as well as in human breast cancer and melanoma samples. Tks5/Fish expression was also required for protease-driven matrigel invasion in human cancer cells. Finally, coexpression of Tks5/Fish and Src in epithelial cells resulted in the appearance of podosomes. Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells.
引用
收藏
页码:155 / 165
页数:11
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