Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Chronic Disease Programme, Madrid, Spain.
Sci Rep. 2019 Jun 27;9(1):9361. doi: 10.1038/s41598-019-45731-w.
Calcium/Calcineurin/Nuclear Factor of Activated T cells (Ca/CN/NFAT) signalling pathway is the main calcium (Ca) dependent signalling pathway involved in the homeostasis of brain tissue. Here, we study the presence of NFATc members in human glioma by using U251 cells and a collection of primary human glioblastoma (hGB) cell lines. We show that NFATc3 member is the predominant member. Furthermore, by using constitutive active NFATc3 mutant and shRNA lentiviral vectors to achieve specific silencing of this NFATc member, we describe cytokines and molecules regulated by this pathway which are required for the normal biology of cancer cells. Implanting U251 in an orthotopic intracranial assay, we show that specific NFATc3 silencing has a role in tumour growth. In addition NFATc3 knock-down affects both the proliferation and migration capacities of glioma cells in vitro. Our data open the possibility of NFATc3 as a target for the treatment of glioma.
钙/钙调神经磷酸酶/活化 T 细胞核因子（Ca/CN/NFAT）信号通路是参与脑组织动态平衡的主要钙（Ca）依赖性信号通路。在这里，我们通过使用 U251 细胞和一系列原发性人神经胶质瘤（hGB）细胞系来研究 NFATc 成员在人神经胶质瘤中的存在。我们表明 NFATc3 成员是主要成员。此外，通过使用组成性激活的 NFATc3 突变体和 shRNA 慢病毒载体来特异性沉默该 NFATc 成员，我们描述了该通路调节的细胞因子和分子，这些分子对于癌细胞的正常生物学是必需的。将 U251 植入原位颅内测定中，我们表明特定的 NFATc3 沉默在肿瘤生长中起作用。此外，NFATc3 敲低在体外影响神经胶质瘤细胞的增殖和迁移能力。我们的数据为 NFATc3 作为神经胶质瘤治疗靶点提供了可能性。
