Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death

M. Stacey Ricci; Seok Hyun Kim; Kazuhiro Ogi; John P. Plastaras; Jianhua Ling; Wenge Wang; Zhaoyu Jin; Yingqiu Y. Liu; David T. Dicker; Paul J. Chiao; Keith T. Flaherty; Charles D. Smith; Wafik S. El-Deiry

doi:10.1016/j.ccr.2007.05.006

Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death

M. Stacey Ricci, Seok Hyun Kim, Kazuhiro Ogi, John P. Plastaras, Jianhua Ling, Wenge Wang, Zhaoyu Jin, Yingqiu Y. Liu, David T. Dicker, Paul J. Chiao, Keith T. Flaherty, Charles D. Smith, Wafik S. El-Deiry

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

226 Scopus citations

Abstract

Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-κB. Both Myc and the multikinase inhibitor sorafenib block NF-κB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.

Original language	English (US)
Pages (from-to)	66-80
Number of pages	15
Journal	Cancer Cell
Volume	12
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2007.05.006
State	Published - Jul 10 2007

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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10.1016/j.ccr.2007.05.006

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Ricci, M. S., Kim, S. H., Ogi, K., Plastaras, J. P., Ling, J., Wang, W., Jin, Z., Liu, Y. Y., Dicker, D. T., Chiao, P. J., Flaherty, K. T., Smith, C. D., & El-Deiry, W. S. (2007). Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death. Cancer Cell, 12(1), 66-80. https://doi.org/10.1016/j.ccr.2007.05.006

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title = "Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death",

abstract = "Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-κB. Both Myc and the multikinase inhibitor sorafenib block NF-κB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.",

author = "Ricci, {M. Stacey} and Kim, {Seok Hyun} and Kazuhiro Ogi and Plastaras, {John P.} and Jianhua Ling and Wenge Wang and Zhaoyu Jin and Liu, {Yingqiu Y.} and Dicker, {David T.} and Chiao, {Paul J.} and Flaherty, {Keith T.} and Smith, {Charles D.} and El-Deiry, {Wafik S.}",

note = "Funding Information: We thank Donna George (University of Pennsylvania) for the Mcl-1 expression vector, Xiaolu Yang (University of Pennsylvania) for the cIAP2 vector, and T.H. Lee for the cIAP2 reporter plasmids (Yonsei University, Seoul, Korea). We also thank Kathryn King and Wendy Weinberg (FDA, Bethesda, MD) for helpful advice regarding NF-κB activation. This work has been presented in part at the 2005 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics during November, 2005 in Philadelphia, PA. M.S.R. received the AACR-Eli Lilly Scholar-in-Training Award for this work. This work was supported in part by NIH grants CA75138, CA98101, CA97100, CA105008, and the Littlefield-AACR award for research on metastatic colon cancer (W.S.E.-D.). ",

year = "2007",

month = jul,

day = "10",

doi = "10.1016/j.ccr.2007.05.006",

language = "English (US)",

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pages = "66--80",

journal = "Cancer Cell",

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T1 - Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death

AU - Ricci, M. Stacey

AU - Kim, Seok Hyun

AU - Ogi, Kazuhiro

AU - Plastaras, John P.

AU - Ling, Jianhua

AU - Wang, Wenge

AU - Jin, Zhaoyu

AU - Liu, Yingqiu Y.

AU - Dicker, David T.

AU - Chiao, Paul J.

AU - Flaherty, Keith T.

AU - Smith, Charles D.

AU - El-Deiry, Wafik S.

N1 - Funding Information: We thank Donna George (University of Pennsylvania) for the Mcl-1 expression vector, Xiaolu Yang (University of Pennsylvania) for the cIAP2 vector, and T.H. Lee for the cIAP2 reporter plasmids (Yonsei University, Seoul, Korea). We also thank Kathryn King and Wendy Weinberg (FDA, Bethesda, MD) for helpful advice regarding NF-κB activation. This work has been presented in part at the 2005 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics during November, 2005 in Philadelphia, PA. M.S.R. received the AACR-Eli Lilly Scholar-in-Training Award for this work. This work was supported in part by NIH grants CA75138, CA98101, CA97100, CA105008, and the Littlefield-AACR award for research on metastatic colon cancer (W.S.E.-D.).

PY - 2007/7/10

Y1 - 2007/7/10

N2 - Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-κB. Both Myc and the multikinase inhibitor sorafenib block NF-κB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.

AB - Cells expressing oncogenic c-Myc are sensitized to TNF superfamily proteins. c-Myc also is an important factor in determining whether a cell is sensitive to TRAIL-induced apoptosis, and it is well established that the mitochondrial pathway is essential for apoptosis induced by c-Myc. We investigated whether c-Myc action on the mitochondria is required for TRAIL sensitivity and found that Myc sensitized cells with defective intrinsic signaling to TRAIL. TRAIL induced expression of antiapoptotic Mcl-1 and cIAP2 through activation of NF-κB. Both Myc and the multikinase inhibitor sorafenib block NF-κB. Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development.

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AN - SCOPUS:34347246278

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JO - Cancer Cell

JF - Cancer Cell

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ER -

Reduction of TRAIL-Induced Mcl-1 and cIAP2 by c-Myc or Sorafenib Sensitizes Resistant Human Cancer Cells to TRAIL-Induced Death

Abstract

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