Downregulation of β-arrestin 1 suppresses glioblastoma cell malignant progression vis inhibition of Src signaling

Exp Cell Res. 2017 Aug 1;357(1):51-58. doi: 10.1016/j.yexcr.2017.04.023. Epub 2017 Apr 22.

Abstract

Glioblastoma multiforme (GBM) is one of the most common brain malignancies worldwide and is typically associated with a dismal prognosis, yet the mechanisms underlying its aggressiveness remain unclear. Here, we revealed that β-arrestin 1 was overexpressed in GBM and contributed to poorer outcome. Knockdown of β-arrestin 1 suppressed the proliferation, invasiveness and glycolysis of GBM cells, and also enhanced temozolomide efficacy. Further, we discovered that knockdown of β-arrestin 1 decreased the activity of Src, and suppression of Src signaling was critically involved in β-arrestin 1 silencing-mediated suppression of GBM malignancies. Finally, we investigated the effect of β-arrestin 1 knockdown on the tumor growth and survival of xenograft models, and found that shβ-arrestin 1 apparently inhibited GBM growth in vivo and resulted in better survival of mice. Taken together, our findings suggest that knockdown of β-arrestin 1 can suppress GBM cell proliferation, invasion and glycolysis by inhibiting Src signaling. Thus, targeting β-arrestin 1 may be a potential therapeutic strategy for GBM treatment.

Keywords: Cell growth; GBM; Glycolysis; Invasion; Src; β-arrestin 1.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Disease Progression
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Mice
  • Neoplasm Invasiveness / pathology
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Signal Transduction* / drug effects
  • Temozolomide
  • beta-Arrestin 1 / metabolism*

Substances

  • ARRB1 protein, human
  • Arrb1 protein, mouse
  • beta-Arrestin 1
  • Dacarbazine
  • Proto-Oncogene Proteins pp60(c-src)
  • Temozolomide