Goicoechea S M, Bednarski B, García-Mata R, Prentice-Dunn H, Kim H J, Otey C A
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Oncogene. 2009 Jan 29;28(4):587-98. doi: 10.1038/onc.2008.408. Epub 2008 Nov 3.
Cancer metastasis involves multiple steps including detachment of the metastatic cells from neighboring cells, the acquisition of motility and invasion to other tissue. All of these steps require the reorganization of the actin cytoskeleton. In this study, we found that the protein palladin, a molecular scaffold with an important function in actin organization, is expressed at higher overall levels in tumors compared with benign breast tissue, and also expressed significantly higher in four invasive breast cancer cell lines when compared with four non-invasive cell lines. In addition, we found that palladin plays a key role in the formation of podosomes. Podosomes are actin-rich structures that function in adhesion and matrix degradation, and have been found in many invasive cell types. Our results show that phorbol ester treatment stimulated the formation of palladin-containing podosomes in invasive, but not in non-invasive cell lines. More importantly, palladin knockdown resulted in decreased podosome formation and a significant reduction in transwell migration and invasive motility. Palladin overexpression induced podosome formation in the non-invasive MCF7 cells, which are otherwise unable to form podosomes, suggesting that palladin plays a critical role in the assembly of podosomes. Overall, these results indicate that palladin overexpression contributes to the invasive behavior of metastatic cells.
癌症转移涉及多个步骤，包括转移细胞与相邻细胞分离、获得运动能力并侵入其他组织。所有这些步骤都需要肌动蛋白细胞骨架的重组。在本研究中，我们发现蛋白 palladin，一种在肌动蛋白组织中具有重要功能的分子支架，与良性乳腺组织相比，在肿瘤中的总体表达水平更高，并且与四种非侵袭性乳腺癌细胞系相比，在四种侵袭性乳腺癌细胞系中的表达也显著更高。此外，我们发现 palladin 在足体的形成中起关键作用。足体是富含肌动蛋白的结构，在黏附和基质降解中起作用，并且已在许多侵袭性细胞类型中发现。我们的结果表明，佛波酯处理刺激了侵袭性细胞系中含 palladin 的足体形成，但在非侵袭性细胞系中未出现这种情况。更重要的是，palladin 敲低导致足体形成减少，以及跨膜迁移和侵袭运动能力显著降低。palladin 过表达在原本无法形成足体的非侵袭性 MCF7 细胞中诱导了足体形成，这表明 palladin 在足体组装中起关键作用。总体而言，这些结果表明 palladin 过表达有助于转移细胞的侵袭行为。
