作者: Masahiro Iwasaki , Sachiko Homma , Akinori Hishiya , Samuel J. Dolezal , John C. Reed
DOI: 10.1158/0008-5472.CAN-07-0618
关键词:
摘要: BAG3 protein binds to and regulates Hsp70 chaperone activity. The contains a WW domain proline-rich region with SH3-binding motifs, suggesting that it may interact proteins relevant signal transduction, recruiting signaling complexes altering cell responses. overexpression has been observed in human cancers. We show here homozygous BAG3-deficient mouse embryonic fibroblasts (MEF) exhibit delayed formation of filopodia focal adhesion when freshly plated. MEFs reduced motility culture. endogenous is highly expressed many epithelial cancer lines, especially adenocarcinomas. Gene transfer-mediated increased Cos7 several including breast MCF7 prostate DU145 ALVA31 lines. Conversely, reduction by RNA interference (RNAi) decreased four tumor lines tested. an influence on In kidney cells, partially colocalizes actin at the leading edge migrating wherein active polymerization nucleation occur. RNAi-mediated reductions expression were associated Rac1 activity, role for regulating this small GTPase involved actin-cytoskeleton dynamics. mice, xenograft suppressed invasion metastasis vivo. Thus, high levels seen some be mechanisms metastasis.