Jones G, Machado J, Merlo A
Molecular Neuro-Oncology Laboratory, Department of Clinical and Biological Sciences, University of Basel, 4031 Basel, Switzerland.
Cancer Res. 2001 Jul 1;61(13):4978-81.
In glioblastoma cells, inhibition of focal adhesion kinase (FAK) by the focal adhesion targeting domain attenuated epidermal growth factor receptor (EGFR) signaling, inhibiting epidermal growth factor-dependent migration. Although the EGFR-specific antagonist PD153035 increased caspase-3 activity, this was independent of FAK activity. Instead, the increase in apoptosis upon inhibition of FAK induced the aggregation of an NH(2)-terminal FAK fragment normally present in the nucleus. A recombinant NH(2)-terminal FAK construct was also targeted to the nucleus and aggregated in apoptotic cells upon coexpression with the focal adhesion targeting domain. Therefore, loss of FAK from the focal adhesions inhibits EGFR signaling at the cell membrane and transmits a proapoptotic signal to an NH(2)-terminal variant of FAK present in the nucleus.
在胶质母细胞瘤细胞中，粘着斑靶向结构域对粘着斑激酶（FAK）的抑制作用减弱了表皮生长因子受体（EGFR）信号传导，从而抑制了表皮生长因子依赖性迁移。尽管EGFR特异性拮抗剂PD153035增加了caspase-3活性，但这与FAK活性无关。相反，抑制FAK后凋亡增加导致通常存在于细胞核中的NH（2）末端FAK片段聚集。重组的NH（2）末端FAK构建体也定位于细胞核，并在与粘着斑靶向结构域共表达时在凋亡细胞中聚集。因此，粘着斑中FAK的缺失抑制了细胞膜上的EGFR信号传导，并向细胞核中存在的FAK的NH（2）末端变体传递促凋亡信号。
