Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Cancer Lett. 2013 Aug 19;336(2):390-7. doi: 10.1016/j.canlet.2013.03.026. Epub 2013 Apr 24.
Store-operated Ca(2+) entry (SOCE) mediates Ca(2+) responses evoked by extracellular signaling molecules to promote increases in cytosolic Ca(2+), thereby triggering downstream signal transduction. Here we demonstrated that either the pharmacological blockage of Ca(2+) influx through SOCE or the knockdown of Orai1, a key molecule of SOCE, suppressed the epidermal growth factor-induced migration by disturbing Ca(2+) signaling in nasopharyngeal carcinoma (NPC) cell. Furthermore, Orai1 depletion led to a delayed cell attachment to the extracellular matrix surface in vitro and eliminated the extravasation of microinjected cells from vasculature in a zebrafish hematogenous metastasis model. Our findings thus indicate that SOCE acts as a predominant Ca(2+) signaling involved in NPC cell metastasis, and may serve as a candidate target for anti-metastasis therapy in NPC.
钙库操纵性钙内流(SOCE)介导细胞外信号分子引发的钙响应,以增加细胞浆内钙离子浓度,从而触发下游信号转导。在这里,我们证明了通过 SOCE 的钙离子内流的药理学阻断或 SOCE 的关键分子奥赖 1(Orai1)的敲低,通过扰乱鼻咽癌细胞中的钙信号,抑制表皮生长因子诱导的迁移。此外,Orai1 耗竭导致细胞在体外附着到细胞外基质表面的延迟,并消除斑马鱼血源性转移模型中小注射细胞从脉管系统中的渗出。因此,我们的研究结果表明 SOCE 作为一种主要的钙信号参与 NPC 细胞转移,并且可能作为 NPC 抗转移治疗的候选靶点。