Pharmacological targeting of Tripartite Motif Containing 24 for the treatment of glioblastoma

J Transl Med. 2021 Dec 9;19(1):505. doi: 10.1186/s12967-021-03158-w.

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor of the central nervous system. Recent studies have reported the crucial functions of Tripartite Motif Containing 24 (TRIM24) in promoting cancer progression of GBM. However, it remains unclear if TRIM24 is an attractive druggable target for therapeutic intervention in GBM. We therefore performed a series of experiments, aiming to verify whether specific TRIM24 inhibition suppresses GBM malignant functions using dTRIM24 and IACS-9571, two novel selective TRIM24 antagonists. Our data showed that TRIM24 inhibitors serve as effective agents for inhibiting cell propagation and invasion of several patient-derived GBM stem cells (GSCs), and these effects are mediated partially through suppression of the TRIM24-SOX2 axis. This study provides novel insight into the TRIM24-based druggable dependencies, important for developing effective therapeutic strategies for brain tumors.

Keywords: Cancer stem cells; Cell Invasion; Cell viability; Glioblastoma; TRIM24.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / pathology
  • Carrier Proteins / antagonists & inhibitors*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Humans
  • Neoplastic Stem Cells / drug effects
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • TRIM24 protein, human