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

Aparna V. Sarthy, Susan E. Morgan-Lappe, Dorothy Zakula, Lawrence Vernetti, Mark Schurdak, Jeremy C.L. Packer, Mark G. Anderson, Senji Shirasawa, Takehiko Sasazuki, Stephen W. Fesik

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65 Citations (Scopus)

Abstract

To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting ∼4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G2-M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin protein.

Original languageEnglish
Pages (from-to)269-276
Number of pages8
JournalMolecular cancer therapeutics
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Sarthy, A. V., Morgan-Lappe, S. E., Zakula, D., Vernetti, L., Schurdak, M., Packer, J. C. L., Anderson, M. G., Shirasawa, S., Sasazuki, T., & Fesik, S. W. (2007). Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells. Molecular cancer therapeutics, 6(1), 269-276. https://doi.org/10.1158/1535-7163.MCT-06-0560