文章：

抑制Rac控制NPM–ALK依赖性淋巴瘤的发展和传播

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

原文发布日期：2011-06-03

DOI: 10.1038/bcj.2011.19

类型: Original Article

开放获取: 是

英文摘要：

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

摘要翻译： 

核仁磷酸蛋白-间变性淋巴瘤激酶（NPM–ALK）是一种酪氨酸激酶癌基因，在大多数人类ALK阳性淋巴瘤的发病机制中起关键作用。我们最近报道了该基因在间变性大细胞淋巴瘤（ALCL）中激活Rac1 GTP酶，进而导致侵袭性所需的活性侵袭足形成。本研究进一步深入探讨该通路，并采用Rac抑制剂NSC23766，通过体外实验、异种移植模型及NPM–ALK转基因小鼠条件模型验证其作为ALCL分子靶点的潜力。研究数据表明，Rac调控NPM–ALK诱导转化的重要效应因子如Erk1/2、p38和Akt。更重要的是，抑制Rac信号传导可阻断NPM–ALK引发的小鼠疾病进展与转移，这凸显了小GTP酶及其调控因子作为淋巴瘤额外治疗靶点的潜力。

原文链接：

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination