Abstract
Angiomotin (Amot) is a newly discovered, multifunctional protein that is involved in cell migration and angiogenesis. However, the role of its isoform, AmotP130, in the regulation of cytoskeleton and metastasis of breast cancer, is unclear. The aim of this study was to investigate the role of AmotP130 in the reorganization of the actin cytoskeleton and the changes of morphology in breast cancer cells through the Rho pathway that influences the invasion and migration of cells. The results suggested that AmotP130 suppressed the invasion ability through remodelling the cytoskeleton of breast cancer cells, including the actin fibre organization and focal adhesion protein turnover. Global transcriptome changes in breast cancer cells following knockdown of AmotP130 identified pathways related with the cytoskeleton and cell motility that involved the Rho GTPase family. From database analyses, changes in the Rho GTPase family of proteins were identified as possible prognostic factors in patients with breast cancer. We have been suggested that AmotP130 suppressed the invasion ability through remodelling of the cytoskeleton of breast cancer cells, involving regulation of the Rho pathway. The cytoskeleton‐related pathway components may provide novel, clinically therapeutic targets for breast cancer treatment.
Highlights
Breast cancer is a major cause of mortality in females
Because global gene expression and pathway analyses indicated that members of the Rho GTPase family participated in some pathways to regulate the cytoskeleton and invasion ability of breast cancer cells, we used western blots to verify RhoA, Rac[1], Cdc[42] and ROCK1protein expression in AmotP130 up- or down-regulated cells (Figure 5A)
The results indicated that Zoledronic acid (ZOL) treatment, which inhibited the Rho signalling pathway, efficiently reversed the effects of knockdown of AmotP130, including the actin fibre polymerization, and increased invasion ability and focal adhesion (FA) formation
Summary
Breast cancer is a major cause of mortality in females. In 2017, there were 40 610 breast cancer-related deaths in US females, second to lung and bronchial cancer.[1]. Angiomotin (Amot), a newly discovered molecule, was identified from its ability to bind to angiostatin using a yeast two-hybrid screening system.[7] Previous studies have demonstrated that Amot is. The role of AmotP130 in the regulation of the cytoskeleton and metastasis of breast cancer is unclear.[11]. The processes could be controlled by the cytoskeleton reorganization and were related to the Rho pathway components
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