BART Inhibits Pancreatic Cancer Cell Invasion by Rac1 Inactivation through Direct Binding to Active Rac1
BART Inhibits Pancreatic Cancer Cell Invasion by Rac1 Inactivation through Direct Binding to Active Rac1
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DOI：
10.1593/neo.12352
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发表时间：
2012-05-01
期刊：
影响因子：
4.8
通讯作者：
Saibara, Toshiji
中科院分区：
文献类型：
--
作者：
Taniuchi, Keisuke;Yokotani, Kunihiko;Saibara, Toshiji
我们报告说，结合剂的Arl两个（BART）在抑制细胞侵袭中发挥作用，通过调节胰腺癌细胞中的Rho小的鸟苷三磷酸酶蛋白Rac 1的活性。BART最初被鉴定为ADP-核糖基化因子样2的结合伴侣，ADP-核糖基化因子样2是一种涉及微管动力学和折叠调节剂的小G蛋白。BART与Rac 1的活性形式相互作用，BART-Rac 1复合物定位于迁移癌细胞的前缘。抑制BART增加活性Rac 1，从而增加细胞侵袭。用Rac 1抑制剂稳定敲除BART的胰腺癌细胞的治疗降低了侵袭性。因此，细胞侵袭的BART依赖性抑制可能与Rac 1活性降低有关。抑制BART诱导膜皱褶和板状伪足突起，并增加板状伪足边缘膜皱褶中的外周肌动蛋白结构。Rac 1抑制剂抑制由抑制BART刺激的板状伪足形成。我们的研究结果表明，BART通过调节Rac 1的活性来调节膜皱褶处的肌动蛋白细胞骨架重排，从而抑制胰腺癌细胞的侵袭。Neoplasia（2012）14，440-450
We report that Binder of Arl Two (BART) plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells. BART was originally identified as a binding partner of ADP-ribosylation factor-like 2, a small G protein implicated as a regulator of microtubule dynamics and folding. BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1. Suppression of BART induces membrane ruffling and lamellipodial protrusion and increases peripheral actin structures in membrane ruffles at the edges of lamellipodia. The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART. Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion. Neoplasia (2012) 14, 440-450