the role of the focal adhesion protein pinch1 for the radiosensitivity of adhesion and suspension cell cultures粘着斑的作用蛋白质pinch1辐射敏感度的附着力和悬浮细胞培养.pdfVIP

The Role of the Focal Adhesion Protein PINCH1 for the Radiosensitivity of Adhesion and Suspension Cell Cultures Veit Sandfort1,3, Iris Eke1,2, Nils Cordes1,2* 1 OncoRay - Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany, 2 Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany, 3 Department of Medicine and Cardiology, Heart Center Dresden University Hospital, Dresden University of Technology, Dresden, Germany Abstract 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 PINCH1fl/fl and PINCH12/ 2 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, p130CAS, Src, AKT, GSK3b 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. Citation: Sandfort V, Eke I, Cordes N (2010) The Role of the Focal Adhesion Protein PINCH1 for the Radiosensitivity of Adhesion and Sus