angiogenin enhances cell migration by regulating stress fiber assembly and focal adhesion dynamics血管生成素增强细胞迁移通过调节压力纤维组装和粘着斑动力学.pdfVIP

Angiogenin Enhances Cell Migration by Regulating Stress Fiber Assembly and Focal Adhesion Dynamics 1 1 2 1 1 Saisai Wei , Xiangwei Gao , Juan Du , Jinfeng Su , Zhengping Xu * 1 Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, China, 2 College of Life Science, Zhejiang University, Hangzhou, China Abstract Angiogenin (ANG) acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, b-actin, a-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with b-actin and a-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research. Citation: Wei S, Gao X, Du J, Su J, Xu Z (2011) Angiogenin Enhances Cell Migration by Regulating Stress Fiber Assembly and Focal Adhesion Dynamics. PLoS ONE 6(12): e28797. doi:10.1371/journal.pone.0028797 Editor: Chr