X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis in Human Cancer Cells

Jordan M. Cummins, Manu Kohli, Carlo Rago, Kenneth W Kinzler, Bert Vogelstein, Fred Bunz

Research output: Contribution to journalArticle

Abstract

Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.

Original languageEnglish (US)
Pages (from-to)3006-3008
Number of pages3
JournalCancer Research
Volume64
Issue number9
DOIs
StatePublished - May 1 2004

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X-Linked Inhibitor of Apoptosis Protein
Tumor Necrosis Factor-alpha
Apoptosis
Inhibitor of Apoptosis Proteins
Ligands
Neoplasms
Immunologic Monitoring
Gene Targeting
Knockout Mice
Technology
Phenotype
Therapeutics
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis in Human Cancer Cells",
abstract = "Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.",
author = "Cummins, {Jordan M.} and Manu Kohli and Carlo Rago and Kinzler, {Kenneth W} and Bert Vogelstein and Fred Bunz",
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T1 - X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Apoptosis in Human Cancer Cells

AU - Cummins, Jordan M.

AU - Kohli, Manu

AU - Rago, Carlo

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Bunz, Fred

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.

AB - Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.

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