CKAP4-mediated activation of FOXM1 via phosphorylation pathways regulates malignant behavior of glioblastoma cells

Kaiyue Xu1, Kaiqian Zhang2, Jiying Ma1

  • 1National Engineering Research Center for Miniaturized Detection Systems, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.

Translational Oncology
|January 26, 2023
PubMed
Abstract

Insights

Cytoskeleton Associated Protein 4 (CKAP4) drives glioblastoma (GBM) malignancy through the FOXM1 pathway. Targeting CKAP4 offers a novel therapeutic strategy and aids in developing prognostic models for glioma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cytoskeleton Associated Protein 4 (CKAP4) is implicated in carcinogenesis, but its precise role in glioblastoma (GBM) remains unclear.
  • Understanding CKAP4's molecular mechanisms in GBM is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the specific role of CKAP4 in the development and progression of Glioblastoma Multiforme (GBM).
  • To identify CKAP4 as a potential therapeutic target and prognostic biomarker for GBM.

Main Methods:

  • Proteomics analysis of GBM versus normal tissues to identify differentially expressed proteins (DEPs).
  • Bioinformatics analysis to identify CKAP4 as a hub gene and develop a prognostic model using Chinese Glioma Genome Atlas (CGGA) data.
  • In vitro and in vivo experiments to assess CKAP4's influence on GBM cell behavior and downstream signaling pathways (FOXM1, AKT, ERK).

Main Results:

  • CKAP4 expression is elevated in GBM, and a CKAP4-based prognostic model accurately predicts patient survival.
  • CKAP4 knockdown suppressed GBM malignancy, while overexpression promoted it in cells and xenograft models.
  • CKAP4 overexpression upregulated FOXM1, AKT, and ERK phosphorylation; inhibiting these pathways synergistically reduced GBM's malignant potential.

Conclusions:

  • This study reveals a novel CKAP4-FOXM1 signaling cascade crucial for GBM's malignant phenotype.
  • The developed CKAP4-based prognostic model can assist in personalized treatment strategies for glioma patients.

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