De Ganck Ariane, De Corte Veerle, Bruyneel Erik, Bracke Marc, Vandekerckhove Joel, Gettemans Jan
Department of Medical Protein Research, VIB, B-9000 Ghent, Belgium.
Int J Oncol. 2009 May;34(5):1403-9.
Enhanced motility of cancer cells by remodelling of the actin cytoskeleton is crucial in the process of cancer cell invasion and metastasis. Although several studies propose a tumor suppressor role for the actin bundling protein myopodin, it was also shown previously that overexpression of mouse myopodin promotes invasion in vitro. In the present study, the role of myopodin in human cancer cell motility and invasion was explored using RNA interference with siRNA duplexes designed to down-regulate all human myopodin isoforms currently identified. We show that down-regulation of myopodin expression in human cancer cells significantly reduces the invasive properties of these cells both in collagen type I and in Matrigel. Furthermore, the motile characteristics of cancer cells are also curbed by reduced myopodin expression whereas cell-cell contacts are reinforced. These results point to a role for myopodin as tumor activator. While these findings are at variance with the suggested tumor suppressor role for myopodin, we hypothesize that the subcellular localization of the protein is involved in its suppressor or activator function in tumorigenesis.
通过重塑肌动蛋白细胞骨架增强癌细胞的运动性在癌细胞侵袭和转移过程中至关重要。尽管多项研究提出肌动蛋白成束蛋白肌动蛋白结合蛋白（myopodin）具有肿瘤抑制作用，但先前也有研究表明，小鼠肌动蛋白结合蛋白的过表达会促进体外侵袭。在本研究中，我们使用RNA干扰技术，设计了针对目前已鉴定的所有人类肌动蛋白结合蛋白异构体的siRNA双链体，以探究肌动蛋白结合蛋白在人类癌细胞运动性和侵袭中的作用。我们发现，下调人类癌细胞中肌动蛋白结合蛋白的表达，会显著降低这些细胞在I型胶原蛋白和基质胶中的侵袭特性。此外，肌动蛋白结合蛋白表达降低会抑制癌细胞的运动特性，同时增强细胞间接触。这些结果表明肌动蛋白结合蛋白具有肿瘤激活剂的作用。虽然这些发现与肌动蛋白结合蛋白所暗示的肿瘤抑制作用不一致，但我们推测该蛋白的亚细胞定位在其肿瘤发生中的抑制或激活功能中起作用。
