AmotP130 regulates Rho GTPase and decreases breast cancer cell mobility

J Cell Mol Med. 2018 Apr;22(4):2390-2403. doi: 10.1111/jcmm.13533. Epub 2018 Jan 29.

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.

Keywords: Rho; angiomotin; breast cancer; cytoskeleton; invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Angiomotins
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cytoskeleton / genetics
  • Female
  • Focal Adhesions / genetics
  • Focal Adhesions / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Membrane Proteins / genetics*
  • Microfilament Proteins
  • Protein Isoforms / genetics
  • Signal Transduction
  • rho GTP-Binding Proteins / genetics*
  • rhoA GTP-Binding Protein / genetics

Substances

  • AMOT protein, human
  • Actins
  • Angiomotins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Protein Isoforms
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein