Abstract：
CASP8 and FADD Like Apoptosis Regulator (CFLAR) is a key anti-apoptotic regulator for resistance to apoptosis mediated by Fas and TRAIL. In addition to its anti-apoptotic function, CFLAR is also an important mediator of tumor growth. High level of CFLAR expression correlates with a more aggressive tumor. However, the mechanism of CFLAR signaling in malignant progression is not clear. Here we report a novel CFLAR-associated protein p130Cas, which is a general regulator of cell growth and cell migration. CFLAR-p130Cas association is mediated by the DED domain of CFLAR and the SD domain of p130Cas. Immunofluorescence observation showed that CFLAR had the colocalization with p130Cas at the focal adhesion of cell membrane. CFLAR overexpression promoted p130Cas phosphorylation and the formation of focal adhesion complex. Moreover, the enhancement of cell migration induced by CFLAR overexpression was obviously inhibited by p130Cas siRNA. In silico analysis on human database suggests high expressions of CFLAR or/and p130Cas are associated with poor prognosis of patients with lung cancer. Together, our results suggest a new mechanism for CFLAR involved in tumor development via association with p130Cas.
摘要：
CASP8和FADD样凋亡调节因子(CFLAR)是抗Fas和TRAIL介导的凋亡的关键抗凋亡调节因子。除了其抗凋亡功能外，CFLAR也是肿瘤生长的重要介质。高水平的CFLAR表达与更具侵袭性的肿瘤相关。然而,CFLAR信号在恶性进展中的作用机制尚不清楚。在这里，我们报道了一种新的CFLAR相关蛋白p130Cas，它是细胞生长和细胞迁移的一般调节剂。CFLAR-p130Cas缔合由CFLAR的DED结构域和p130Cas的SD结构域介导。免疫荧光观察显示，CFLAR与p130Cas在细胞膜粘附灶处具有共定位。CFLAR过表达促进p130Cas磷酸化和粘着斑复合物的形成。此外，p130CassiRNA明显抑制CFLAR过表达诱导的细胞迁移增强。人类数据库的计算机模拟分析表明CFLAR或/和p130Cas的高表达与肺癌患者的不良预后相关。一起,我们的结果提示CFLAR通过与p130Cas相关参与肿瘤发展的新机制.
