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p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies

Seth A Wander1, Dekuang Zhao, Joyce M Slingerland

  • 1Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 23, 2010
PubMed

Insights

The cyclin-dependent kinase inhibitor p27's function is disrupted in human cancers by oncogenic signaling pathways. This deregulation, through altered stability and localization, drives cancer progression and offers therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • The cyclin-dependent kinase inhibitor p27 (also known as CDKN1B) is a crucial regulator of cell cycle progression.
  • Mitogenic signaling pathways influence p27's stability, cellular localization, and overall biological activity.
  • Dysregulation of p27 contributes to uncontrolled cell proliferation and migration in human cancers.

Purpose of the Study:

  • To review the mechanisms by which oncogenic signaling pathways deregulate the function of p27.
  • To highlight the implications of p27 functional loss in human cancer development.
  • To establish a molecular rationale for targeting signaling pathways in cancer therapy.

Main Methods:

  • Literature review of studies investigating p27 phosphorylation and its downstream effects.
  • Analysis of signaling pathways that impact p27 stability and localization.
  • Examination of the role of p27 deregulation in various human cancers.

Main Results:

  • Phosphorylation by mitogenic pathways alters p27 stability and localization.
  • Reduced p27 protein levels lead to increased cell proliferation.
  • Cytoplasmic mislocalization of p27 promotes cell migration.
  • These alterations in p27 function are observed across multiple human cancer types.

Conclusions:

  • Functional deregulation of p27 by oncogenic signaling is a significant factor in cancer progression.
  • Altered p27 levels and localization contribute to both increased proliferation and migration.
  • Targeting specific oncogenic signaling pathways offers a promising therapeutic strategy for cancers exhibiting p27 dysfunction.

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