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PTEN suppresses SPARC-induced pMAPKAPK2 and inhibits SPARC-induced Ser78 HSP27 phosphorylation in glioma

Ridwan Alam1, Chad R Schultz, William A Golembieski

  • 1Barbara Jane Levy Laboratory of Molecular Neuro-Oncology, Hermelin Brain Tumor Center, Department of Neurosurgery, Education and Research Bldg., Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.

Neuro-Oncology
|February 6, 2013
PubMed
Abstract

Insights

Secreted protein acidic and rich in cysteine (SPARC) promotes glioma migration. Phosphatase and tensin homolog (PTEN) suppresses this by inhibiting the P38 MAPK-MAPKAPK2-HSP27 pathway, revealing a novel anti-migration mechanism.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Cancer research

Background:

  • Secreted protein acidic and rich in cysteine (SPARC) is overexpressed in astrocytomas (WHO grades II-IV).
  • SPARC promotes glioma cell migration and invasion via the P38 MAPK-HSP27 pathway.
  • The tumor suppressor phosphatase and tensin homolog (PTEN) inhibits SPARC-induced migration by affecting Akt and ERK signaling.

Purpose of the Study:

  • To investigate the effect of PTEN expression on SPARC-induced heat shock protein 27 (HSP27) expression and phosphorylation.
  • To elucidate the role of PTEN in regulating the P38 MAPK-MAPKAPK2-HSP27 signaling pathway in the context of SPARC-driven glioma migration.

Main Methods:

  • Utilized control and SPARC-expressing astrocytoma cell lines, transfected with either control or PTEN-expression plasmids.
  • Cells were cultured on fibronectin-coated plates for varying durations (3-48 hours).
  • Protein expression and phosphorylation levels were analyzed using Western blot and densitometry.

Main Results:

  • SPARC increased phosphorylation of P38 MAPK, MAPKAPK2, and HSP27 (Ser78).
  • PTEN suppressed Akt and MAPKAPK2 phosphorylation, indicating effects downstream of P38 MAPK.
  • PTEN inhibited SPARC-induced sustained phosphorylation of HSP27 at Ser78, even with increased total HSP27 levels.

Conclusions:

  • PTEN suppresses SPARC-induced glioma cell migration.
  • PTEN exerts its inhibitory effect through differential regulation of the P38 MAPK-MAPKAPK2-HSP27 signaling pathway.
  • This study identifies a novel mechanism by which PTEN antagonizes SPARC-driven glioma progression.

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