Identification of a Druggable Pathway Controlling Glioblastoma Invasiveness

Cell Rep. 2017 Jul 5;20(1):48-60. doi: 10.1016/j.celrep.2017.06.036.


Diffuse and uncontrollable brain invasion is a hallmark of glioblastoma (GBM), but its mechanism is understood poorly. We developed a 3D ex vivo organotypic model to study GBM invasion. We demonstrate that invading GBM cells upregulate a network of extracellular matrix (ECM) components, including multiple collagens, whose expression correlates strongly with grade and clinical outcome. We identify interferon regulatory factor 3 (IRF3) as a transcriptional repressor of ECM factors and show that IRF3 acts as a suppressor of GBM invasion. Therapeutic activation of IRF3 by inhibiting casein kinase 2 (CK2)-a negative regulator of IRF3-downregulated the expression of ECM factors and suppressed GBM invasion in ex vivo and in vivo models across a panel of patient-derived GBM cell lines representative of the main molecular GBM subtypes. Our data provide mechanistic insight into the invasive capacity of GBM tumors and identify a potential therapy to inhibit GBM invasion.

Keywords: casein kinase 2; collagen; extracellular matrix; glioblastoma; interferon regulatory factor 3; invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Neoplasm Invasiveness


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Casein Kinase II