The Role of the Focal Adhesion Protein PINCH1 for the Radiosensitivity of Adhesion and Suspension Cell Cultures
The Role of the Focal Adhesion Protein PINCH1 for the Radiosensitivity of Adhesion and Suspension Cell Cultures
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DOI：
10.1371/journal.pone.0013056
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发表时间：
2010-09-28
期刊：
影响因子：
3.7
通讯作者：
Cordes, Nils
中科院分区：
文献类型：
--
作者：
Sandfort, Veit;Eke, Iris;Cordes, Nils
粘着斑信号通过与细胞外基质和生长因子受体的粘附而参与调节细胞对外界刺激的应激反应。对局灶性黏附组装和信号转导至关重要的是接头蛋白PINCH1。为了评估PINCH1在辐射细胞存活中的生存功能是否依赖于细胞黏附，我们研究了PINCH1(f1/fl)和PINCH1(-/-)小鼠胚胎成纤维细胞和人类癌细胞系。在这里，我们发现，当细胞在悬浮条件下照射时，在黏附条件下观察到的由PINCH1耗竭所介导的细胞辐射敏感性的增强是保守的。这一意外发现不能用观察到的粘着和生长因子相关信号的改变来解释，这些信号涉及FAK、paxlin、p130(CAS)、Src、AKT、GSK3β和ERK1/2在悬液和血清撤除条件下相对于与血清的粘连条件。我们的数据表明，在黏附和悬浮条件下，适配蛋白PINCH1同样关键地参与了正常和恶性细胞的细胞辐射敏感性的调节。
Focal adhesion (FA) signaling mediated by adhesion to extracellular matrix and growth factor receptors contributes to the regulation of the cellular stress response to external stimuli. Critical to focal adhesion assembly and signaling is the adapter protein PINCH1. To evaluate whether the prosurvival function of PINCH1 in radiation cell survival depends on cell adhesion, we examined PINCH1(fl/fl) and PINCH1(-/-) mouse embryonic fibroblasts and human cancer cell lines. Here, we found that the enhanced cellular radiosensitivity mediated by PINCH1 depletion observed under adhesion conditions is conserved when cells are irradiated under suspension conditions. This unsuspected finding could not be explained by the observed modification of adhesion and growth factor associated signaling involving FAK, Paxillin, p130(CAS), Src, AKT, GSK3 beta and ERK1/2 under suspension and serum withdrawal relative to adhesion conditions with serum. Our data suggest that the adapter protein PINCH1 critically participates in the regulation of the cellular radiosensitivity of normal and malignant cells similarly under adhesion and suspension conditions.