Radixin knockdown by RNA interference suppresses human glioblastoma cell growth in vitro and in vivo

Asian Pac J Cancer Prev. 2014;15(22):9805-12. doi: 10.7314/apjcp.2014.15.22.9805.

Abstract

Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or non- sense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation*
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Glioblastoma / prevention & control*
  • Humans
  • Immunoenzyme Techniques
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Cadherins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Thrombospondin 1
  • radixin