Ezrin promotes breast cancer progression by modulating AKT signals

Br J Cancer. 2019 Apr;120(7):703-713. doi: 10.1038/s41416-019-0383-z. Epub 2019 Feb 26.

Abstract

Background: Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear.

Methods: Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression.

Results: In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC.

Conclusions: In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Disease Progression
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction

Substances

  • Cytoskeletal Proteins
  • ezrin
  • Proto-Oncogene Proteins c-akt