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Role of STAT3 in in vitro transformation triggered by TRK oncogenes

Claudia Miranda1, Tiziana Fumagalli, Maria Chiara Anania

  • 1Operative Unit Molecular Mechanisms, Department of Experimental Oncology and Molecular Medicine, IRCCS Foundation, Istituto Nazionale dei Tumori, Milan, Italy. claudia.miranda@istitutotumori.mi.it

Plos One
|March 9, 2010
PubMed

Insights

TRK oncogenes activate STAT3 signaling, but paradoxically decrease STAT3 protein levels, which drives NIH3T3 cell transformation. Residual STAT3 activity is essential for cell growth in TRK-transformed cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • TRK oncoproteins, derived from NTRK1/NGF receptor, exhibit constitutive tyrosine kinase activity.
  • Signal Transducer and Activator of Transcription (STAT) 3 is a key mediator in cytokine and growth factor signaling.
  • STAT3 has been identified as a novel signal transducer for TrkA, crucial for nerve growth factor (NGF) functions.

Purpose of the Study:

  • To investigate the role of STAT3 in signaling pathways activated by TRK oncogenes.
  • To elucidate the dual function of STAT3 in TRK-driven NIH3T3 cell transformation.

Main Methods:

  • Analysis of STAT3 phosphorylation at Y705 and S727 residues.
  • Assessment of STAT3 transcriptional activity.
  • Investigation of MAPK pathway involvement in STAT3 phosphorylation.
  • Quantification of STAT3 protein levels in transformed cells.

Main Results:

  • TRK oncogenes induce STAT3 phosphorylation and transcriptional activity.
  • The MAPK pathway is implicated in STAT3 phosphorylation.
  • A decrease in STAT3 protein levels was observed in TRK-oncogene-expressing NIH3T3 transformed cells.
  • TRK oncoprotein activity correlates with reduced STAT3 protein levels and morphological transformation.

Conclusions:

  • STAT3 plays a dual role in TRK oncogene-induced NIH3T3 transformation.
  • Reduced STAT3 protein levels contribute to morphological transformation.
  • Sustained STAT3 transcriptional activity is necessary for cell proliferation in this context.

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