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Survivin is a novel target of CD44-promoted breast tumor invasion

Mohamed E Abdraboh1, Rajiv L Gaur, Andrew D Hollenbach

  • 1Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman.

The American Journal of Pathology
|July 2, 2011
PubMed

Insights

Hyaluronan receptor CD44 promotes breast cancer invasion by increasing survivin expression. This study reveals the PI3K/E2F1 pathway links CD44 activation to survivin transcription, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The hyaluronan (HA) receptor CD44 is crucial for cell communication and signaling.
  • CD44's role in breast cancer (BC) metastasis is established, but underlying mechanisms require elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms by which CD44 influences breast cancer cell invasion.
  • To identify downstream targets of CD44 signaling in breast cancer progression.

Main Methods:

  • Utilized a tetracycline-off-regulated CD44 expression system in MCF-7 cells.
  • Employed microarray analysis to identify CD44 transcriptional targets.
  • Combined molecular and pharmacologic approaches to validate findings.
  • Analyzed clinical breast tissue samples for CD44 and survivin (SVV) expression.

Main Results:

  • Identified survivin (SVV) as a downstream transcriptional target of CD44.
  • Demonstrated that CD44 induction upregulates SVV expression, promoting BC cell invasion.
  • Observed parallel expression patterns of SVV and standard CD44 during breast tumor progression.
  • Uncovered the PI3K/E2F1 pathway as a molecular link between HA/CD44 activation and SVV transcription.

Conclusions:

  • SVV is a key mediator of CD44-driven breast cancer cell invasion.
  • The PI3K/E2F1 pathway is implicated in the regulation of SVV by HA/CD44 signaling.
  • Findings enhance understanding of SVV's function in breast cancer metastasis and suggest potential therapeutic strategies.

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