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Shp2 suppresses PyMT-induced transformation in mouse fibroblasts by inhibiting Stat3 activity

Ying Yang1, Beibei Jiang, Yingqing Huo

  • 1Laboratory of Vascular Biology, Institute of Molecular Medicine, Peking University, Beijing 100871, China. yingyang76@gmail.com

Virology
|November 9, 2010
PubMed

Insights

Protein tyrosine phosphatase Shp2 suppresses transformation induced by mouse polyoma virus middle T antigen (PyMT). Shp2

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Protein tyrosine phosphatase Shp2 has paradoxical roles, acting as an oncogene in leukemia but with dominant-negative mutations also found in cancers.
  • Mouse polyoma virus middle T antigen (PyMT) is a viral oncoprotein that induces cell transformation, often via pp60(c-src) activation.

Purpose of the Study:

  • To investigate the role of Shp2 in PyMT-induced cell transformation.
  • To elucidate the mechanism by which Shp2 influences transformation mediated by PyMT.

Main Methods:

  • Over-expression of wild-type and catalytically inactive Shp2 mutants in NIH3T3 cells.
  • Re-introduction of Shp2 into Shp2-deficient cells.
  • Short hairpin RNA (shRNA)-mediated knockdown of Shp2.
  • Assessment of PyMT-induced transformation and tumorigenesis.
  • Analysis of signal transducers and activators of transcription 3 (STAT3) pathway.

Main Results:

  • Over-expression of a catalytically inactive Shp2 mutant enhanced PyMT-induced transformation.
  • Restoring Shp2 in deficient cells inhibited PyMT-induced transformation and tumorigenesis.
  • Shp2 knockdown potentiated PyMT-induced transformation.
  • Shp2's suppressive effects on transformation are partly mediated by inhibiting STAT3.

Conclusions:

  • Shp2 acts as a tumor suppressor in the context of PyMT-induced transformation.
  • The inhibitory effect of Shp2 on transformation involves the suppression of the STAT3 signaling pathway.

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