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PI3K and STAT3: a new alliance

Peter K Vogt1, Jonathan Ross Hart

  • 1The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. pkvogt@scripps.edu

Cancer Discovery
|February 21, 2012
PubMed
Abstract

Insights

The PI3K and STAT3 pathways are linked, with BMX kinase mediating STAT3 activation in PI3K-driven cancers like glioblastoma. Targeting BMX may enhance PI3K inhibitor effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Proteomic data reveal an interdependence between Phosphoinositide 3-kinase (PI3K) and Signal transducer and activator of transcription 3 (STAT3) signaling pathways.
  • STAT3 phosphorylation and activation are PI3K-dependent in transformed murine cells, suggesting a functional link between these pathways.

Purpose of the Study:

  • To investigate the role of STAT3 and the TEC kinase BMX in PI3K-driven oncogenesis.
  • To explore BMX as a potential therapeutic target in cancers involving PI3K and STAT3 signaling.

Main Methods:

  • Analysis of PI3K-transformed murine cells to assess STAT3 phosphorylation and activation.
  • Utilizing dominant-negative STAT3 to evaluate its role in PI3K-induced transformation.
  • Investigating the involvement of the TEC kinase BMX in STAT3 phosphorylation.
  • Examining the roles of STAT3 and BMX in glioblastoma stem cells.

Main Results:

  • STAT3 is phosphorylated on Y705 and activated in a PI3K-dependent manner in transformed murine cells.
  • STAT3 plays a critical role in PI3K-induced oncogenic transformation.
  • The TEC kinase BMX mediates STAT3 phosphorylation in PI3K-transformed cells.
  • STAT3 and BMX exhibit similar critical roles in glioblastoma stem cells.

Conclusions:

  • A functional link exists between the PI3K–TOR and STAT3 signaling pathways.
  • STAT3 is crucial for PI3K-driven oncogenic transformation.
  • The TEC kinase BMX is identified as a novel therapeutic target for enhancing PI3K inhibitor efficacy in cancer treatment.
Keywords:
BMXPH domainSILACTEC kinaseTOR

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