Angiogenin Enhances Cell Migration by Regulating Stress Fiber Assembly and Focal Adhesion Dynamics

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, β-actin, α-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 β-actin and α-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.

Profilin-1 Serves as a Gatekeeper for Actin Assembly by Arp2/3-Dependent and -Independent Pathways

“…Analysis was done similarly to already established approaches (Wei et al, 2011). A full description can be found in the supplemental experimental procedures.…”

Three decades of research on angiogenin: a review and perspective

“…Thus, ANG may promote degradation of the basement membrane and extracellular matrix, thus allowing endothelial cells to penetrate and migrate. In addition, our laboratory has demonstrated that cytoplasmic ANG optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration by interacting with β-actin, α-actinin 4, and nonmuscle myosin heavy chain 9 [98].…”

Alpha-Actinin 4 and Tumorigenesis of Breast Cancer

“…Metastasis is a complicated process in which distal tumor dissemination occurs after cancer cells in the primary tumor experience epithelial–mesenchymal transition (EMT) to disrupt intercellular junctions, reorganize the actin cytoskeleton, and increase cell motility for initial cancer cell spreading (Sarrió et al, 2008). Several stromal and endocrine growth factors, including insulin-like growth factor I (IGF-1), fibroblast growth factor, EGF, and angiogenin (ANG), regulate ACTN or ACTN4 binding to its cytoskeletal working partners and hence result in cell morphological changes and cytoskeletal reorganization, both of which may facilitate the metastatic process (Guvakova, Adams, & Boettiger, 2002; Shao, Wu, et al, 2010; Vandermoere et al, 2007; Wei, Gao, Du, Su, & Xu, 2011). In most breast cancers, the separation of invasive carcinoma from nearby adherent epithelium is an early step for metastases.…”