EGFRvIII Promotes the Proneural-Mesenchymal Transition of Glioblastoma Multiforme and Reduces Its Sensitivity to Temozolomide by Regulating the NF-κB/ALDH1A3 Axis

Genes (Basel). 2023 Mar 4;14(3):651. doi: 10.3390/genes14030651.

Abstract

(1) Background: Glioblastoma multiforme (GBM) is the most common and malignant intracranial tumor in adults. At present, temozolomide (TMZ) is recognized as the preferred chemotherapeutic drug for GBM, but some patients have low sensitivity to TMZ or chemotherapy resistance to TMZ. Our previous study found that GBM patients with EGFRvIII (+) have low sensitivity to TMZ. However, the reasons and possible mechanisms of the chemoradiotherapy resistance in GBM patients with EGFRvIII (+) are not clear. (2) Methods: In this study, tissue samples of patients with GBM, GBM cell lines, glioma stem cell lines, and NSG mice were used to explore the causes and possible mechanisms of low sensitivity to TMZ in patients with EGFRvIII (+)-GBM. (3) Results: The study found that EGFRvIII promoted the proneural-mesenchymal transition of GBM and reduced its sensitivity to TMZ, and EGFRvIII regulated of the expression of ALDH1A3. (4) Conclusions: EGFRvIII activated the NF-κB pathway and further regulated the expression of ALDH1A3 to promote the proneural-mesenchymal transition of GBM and reduce its sensitivity to TMZ, which will provide an experimental basis for the selection of clinical drugs for GBM patients with EGFRvIII (+).

Keywords: ALDH1A3; EGFRvIII; NF-κB; glioblastoma; proneural–mesenchymal transition; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Mice
  • NF-kappa B / genetics
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Temozolomide
  • epidermal growth factor receptor VIII
  • NF-kappa B

Grants and funding

This work was supported by the National Natural Science Foundation of China (82072768), the Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences (2020-I2M-C&T-A-024), the Sino-German Center Cooperation and Exchanges Program (M-0020), and the public welfare development and reform pilot project of Beijing Medical Research Institute (JYY 2022–7).