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Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells

Aparna V Sarthy1, Susan E Morgan-Lappe, Dorothy Zakula

  • 1Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. aparna.sarthy@abbott.com

Molecular Cancer Therapeutics
|January 24, 2007
PubMed

Insights

This study identified survivin as a potential cancer target. Targeting survivin (baculoviral inhibitor of apoptosis repeat-containing 5) effectively reduced survival in colon cancer cells with activated K-Ras.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Activated K-Ras oncogene drives colon carcinoma progression.
  • Identifying synthetic lethal targets is crucial for cancer therapy.

Purpose of the Study:

  • To discover novel cancer-specific targets through a synthetic lethal screen.
  • To evaluate the role of survivin in K-Ras-driven colon cancer.

Main Methods:

  • Conducted a small interfering RNA (siRNA) screen of ~4,000 genes.
  • Utilized DLD-1 colon carcinoma cells with activated K-Ras and a disrupted counterpart (DKS-8).
  • Assessed cell survival, cell cycle progression, polyploidy, and caspase-3 activation.

Main Results:

  • siRNAs targeting survivin (baculoviral inhibitor of apoptosis repeat-containing 5) significantly reduced survival in activated K-Ras cells.
  • Survivin siRNA induced G(2)-M arrest and polyploidy.
  • Increased caspase-3 activation was observed in K-Ras-transformed cells treated with survivin siRNA.

Conclusions:

  • Tumors with activated K-Ras oncogenes are particularly sensitive to survivin inhibition.
  • Survivin represents a promising therapeutic target for K-Ras-driven cancers.

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