TGF-β Signaling Promotes Glioma Progression Through Stabilizing Sox9

Front Immunol. 2021 Feb 3:11:592080. doi: 10.3389/fimmu.2020.592080. eCollection 2020.

Abstract

Gliomas are brain and spinal cord malignancies characterized by high malignancy, high recurrence and poor prognosis, the underlying mechanisms of which remain largely elusive. Here, we found that the Sry-related high mobility group box (Sox) family transcription factor, Sox9, was upregulated and correlated with poor prognosis of clinical gliomas. Sox9 promotes migration and invasion of glioma cells and in vivo development of xenograft tumors from inoculated glioma cells. Sox9 functions downstream of the transforming growth factor-β (TGF-β) pathway, in which TGF-β signaling prevent proteasomal degradation of the Sox9 protein in glioma cells. These findings provide novel insight into the wide interplay between TGF-β signaling and oncogenic transcription factors, and have implications for targeted therapy and prognostic assessment of gliomas.

Keywords: Sox9; glioma; invasion; migration; transforming growth factor-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / etiology*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Disease Progression
  • Disease Susceptibility
  • Gene Expression
  • Gene Knockdown Techniques
  • Glioma / etiology*
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Immunohistochemistry
  • Mice
  • Protein Binding
  • Protein Stability
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Tumor Cells, Cultured

Substances

  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Transforming Growth Factor beta