The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
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DOI：
10.1016/j.ccr.2005.01.006
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发表时间：
2005-02-01
期刊：
影响因子：
50.3
通讯作者：
Courtneidge, SA
中科院分区：
文献类型：
--
作者：
Seals, DF;Azucena, EF;Courtneidge, SA
Tks5/Fish是一种具有5个SH3结构域和1个PX结构域的支架蛋白。在src转化的细胞中，Tks5/Fish定位于足质体，腹膜的离散突起。我们生成了Tks5/Fish水平降低的src转化细胞。它们不再形成足质体，不降解明胶，侵入性差。我们检测到Tks5/Fish在侵袭性癌细胞、乳腺癌和黑色素瘤样本的足小体中表达。Tks5/Fish在蛋白酶驱动的基质侵袭人类癌细胞中也需要表达。最后，上皮细胞中Tks5/Fish和Src的共表达导致了足小体的出现。因此，Tks5/Fish似乎是足小体形成、细胞外基质降解和某些癌细胞侵袭所必需的。
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.