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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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Tumor cell migration and invasion are enhanced by depletion of Rap1 GTPase-activating protein (Rap1GAP)

Oxana M Tsygankova1, Hongbin Wang, Judy L Meinkoth

  • 1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6061, USA.

The Journal of Biological Chemistry
|July 19, 2013
PubMed

Insights

Loss of Rap1 GTPase-activating protein (Rap1GAP) in colon cancer cells increases their aggressive migration and invasion. This occurs by altering cell motility mechanisms, highlighting Rap1GAP

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Rap1 GTPase-activating protein (Rap1GAP) is frequently downregulated in human tumors.
  • The functional role of Rap1GAP in tumor progression remains largely unknown.

Purpose of the Study:

  • To investigate the functional significance of Rap1GAP downregulation in human colon cancer.
  • To elucidate the molecular mechanisms by which Rap1GAP affects tumor cell migration and invasion.

Main Methods:

  • Gene silencing of Rap1GAP in human colon cancer cells.
  • Assessment of cell migration and invasion assays.
  • Analysis of Rap1, ROCK, and Rac1 activity.
  • Cell morphology and membrane protrusion analysis.

Main Results:

  • Rap1GAP depletion significantly enhanced colon cancer cell migration and invasion.
  • Silencing Rap1GAP increased endogenous Rap activity and altered cell morphology.
  • Loss of Rap1GAP shifted migratory mechanisms towards Rac1-dependent pathways, suppressing ROCK activity.
  • Inhibition of Rac1 restored ROCK activity and membrane blebbing in Rap1GAP-depleted cells.

Conclusions:

  • Rap1GAP is a critical regulator of aggressive tumor cell behavior.
  • Downregulation of Rap1GAP promotes tumor cell invasion and metastasis.
  • Rap1GAP levels influence the choice between different cell migratory mechanisms in cancer.
Keywords:
Cancer BiologyCell InvasionCell MotilityColon CancerMigrationRacRapRap1GAP

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