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Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression

Samuel Godar1, Tan A Ince, George W Bell

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Cell
|July 11, 2008
PubMed

Insights

The p53 tumor suppressor protein inhibits CD44 expression under stress. Loss of p53 function promotes tumor growth by increasing CD44 levels, highlighting CD44 as a tumor promoter.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The p53 tumor suppressor is crucial for cellular stress responses.
  • CD44 is a cell-surface molecule involved in cell adhesion and migration.
  • Dysregulation of p53 and CD44 is implicated in cancer development.

Purpose of the Study:

  • To investigate the regulatory relationship between p53 and CD44 expression.
  • To determine the role of CD44 in p53-deficient tumor cells.
  • To explore the implications of this interaction in cancer progression.

Main Methods:

  • Analysis of p53 binding to the CD44 promoter.
  • Measurement of CD44 expression in cells with varying p53 function.
  • Assessment of cell growth and tumor-initiating ability.

Main Results:

  • p53 directly inhibits CD44 expression by binding to its promoter.
  • Loss of p53 function leads to increased CD44 expression.
  • Elevated CD44 is essential for the growth of p53-deficient mammary tumor cells.
  • CD44 expression is positively regulated by p63, a p53 paralogue.

Conclusions:

  • CD44 acts as a tumor promoter in cells lacking p53.
  • Inactivation of p53 and subsequent CD44 derepression may facilitate premalignant cell survival.
  • Targeting CD44 could be a therapeutic strategy for p53-mutated cancers.

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