The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer

Nachmias, Boaz; Ashhab, Yaqoub; Ben‐Yehuda, Dina

doi:10.1016/j.semcancer.2004.04.002

Cited by 235 publications

(200 citation statements)

References 127 publications

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“…24,25 Livin, also called melanoma IAP or kidney IAP, is a novel member of human IAP family members. Previous reports have indicated that Livin is low expressed or not expressed in human normal tissues, but it is upregulated in a variety of human cancers.…”

Section: Discussionmentioning

confidence: 99%

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

et al. 2008

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Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G 1 /G 0 phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers.

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Section: Discussionmentioning

confidence: 99%

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

et al. 2008

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“…The human IAP family proteins, which include c-IAP1, c-IAP2, NAIP, Survivin, XIAP, Bruce, ILP-2 and Livin, are potent inhibitors of apoptosis and potentially involved in human cancer formation (see, Salvesen and Duckett, 2002;Nachmias et al, 2004, for reviews). These proteins are highly conserved from fly to human.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis

Yuan

Zhuo

et al. 2005

Oncogene

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“…One of the hallmark features of cancer is the ability to evade apoptosis, particularly by up-regulation of antiapoptotic genes such as certain members of the Bcl-2 family of proteins (2) and the inhibitor of apoptosis (IAP) family of proteins (3). IAPs, particularly cellular IAP1 (cIAP1), cIAP2, and X-linked IAP (XIAP), function to prevent cell death by preventing activation of caspase-8 or inhibiting the activity of caspases-9, -3, and -7, respectively (4-6).…”

mentioning

confidence: 99%

Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression

Petersen

Peyton

Minna

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

105

107

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Smac mimetics target cancer cells in a TNFα-dependent manner, partly via proteasome degradation of cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2. Degradation of cIAPs triggers the release of receptor interacting protein kinase (RIPK1) from TNF receptor I (TNFR1) to form a caspase-8 activating complex together with the adaptor protein Fas-associated death domain (FADD). We report here a means through which cancer cells mediate resistance to Smac mimetic/TNFα-induced apoptosis and corresponding strategies to overcome such resistance. These human cancer cell lines evades Smac mimetic-induced apoptosis by up-regulation of cIAP2, which although initially degraded, rebounds and is refractory to subsequent degradation. cIAP2 is induced by TNFα via NF-κB and modulation of the NF-κB signal renders otherwise resistant cells sensitive to Smac mimetics. In addition, other signaling pathways, including phosphatidyl inositol-3 kinase (PI3K), have the potential to concurrently regulate cIAP2. Using the PI3K inhibitor, LY294002, cIAP2 up-regulation was suppressed and resistance to Smac mimetics-induced apoptosis was also overcome.

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The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer

Cited by 235 publications

References 127 publications

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene expression and confer resistance to apoptosis

Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression

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