Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target

Cancer Res. 2013 Mar 1;73(5):1559-69. doi: 10.1158/0008-5472.CAN-12-1943. Epub 2012 Dec 13.


Glioblastoma is the most common form of primary adult brain tumors. A majority of glioblastomas grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control glioblastoma invasiveness and target them therapeutically. We show here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of glioblastoma cell lines and primary glioblastoma cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathologic grades in patient biopsies. Id-1 knockdown dramatically reduces glioblastoma cell invasion that is accompanied by profound morphologic changes and robust reduction in expression levels of "mesenchymal" markers, as well as inhibition of self-renewal potential and downregulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human glioblastoma. Furthermore, we show that a nontoxic compound, cannabidiol, significantly downregulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. In addition, cannabidiol significantly inhibits the invasion of glioblastoma cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in glioblastoma and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of patients with glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cannabidiol / pharmacology
  • Cell Line, Tumor
  • Female
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Inhibitor of Differentiation Protein 1 / antagonists & inhibitors
  • Inhibitor of Differentiation Protein 1 / metabolism
  • Inhibitor of Differentiation Protein 1 / physiology*
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / genetics*
  • Neurospora
  • RNA Interference
  • Transplantation, Heterologous
  • Up-Regulation


  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • Cannabidiol