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

doi:10.1158/1535-7163.MCT-06-0560

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

Research output: Contribution to journal › Article › peer-review

71 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 language	English
Pages (from-to)	269-276
Number of pages	8
Journal	Molecular cancer therapeutics
Volume	6
Issue number	1
DOIs	https://doi.org/10.1158/1535-7163.MCT-06-0560
Publication status	Published - Jan 2007
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1535-7163.MCT-06-0560

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title = "Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells",

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.",

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AU - Sarthy, Aparna V.

AU - Morgan-Lappe, Susan E.

AU - Zakula, Dorothy

AU - Vernetti, Lawrence

AU - Schurdak, Mark

AU - Packer, Jeremy C.L.

AU - Anderson, Mark G.

AU - Shirasawa, Senji

AU - Sasazuki, Takehiko

AU - Fesik, Stephen W.

PY - 2007/1

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N2 - 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.

AB - 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.

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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