Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo

Abstract

Radixin, a member of the ERM (ezrin–radixin–moesin) family, plays important roles in cell motility, invasionand tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types ofepithelial 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-mediatedshort-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastomaU251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cellswere implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsenseshRNA 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, MMP9was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration andinvasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.