Seals Darren F, Azucena Eduardo F, Pass Ian, Tesfay Lia, Gordon Rebecca, Woodrow Melissa, Resau James H, Courtneidge Sara A
Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.
Cancer Cell. 2005 Feb;7(2):155-65. doi: 10.1016/j.ccr.2005.01.006.
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.
Tks5/Fish是一种具有五个SH3结构域和一个PX结构域的支架蛋白。在Src转化的细胞中，Tks5/Fish定位于足体，即腹侧膜的离散突起。我们构建了Tks5/Fish水平降低的Src转化细胞。这些细胞不再形成足体，不能降解明胶，且侵袭能力较差。我们在侵袭性癌细胞的足体中以及人乳腺癌和黑色素瘤样本中检测到了Tks5/Fish的表达。人癌细胞中蛋白酶驱动的基质胶侵袭也需要Tks5/Fish的表达。最后，上皮细胞中共表达Tks5/Fish和Src会导致足体的出现。因此，Tks5/Fish似乎是足体形成、细胞外基质降解以及某些癌细胞侵袭所必需的。
