Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

Novak, Rachel; Phillips, Andrew C.

doi:10.1038/cgt.2008.25

Cited by 27 publications

(31 citation statements)

References 28 publications

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“…RYBP (RING1 and YY1 binding protein, also known as DEDAF) functions as a repressor of E4TF1 and induces apoptosis in tumour cells (Danen-van Oorschot et al 2004). The preferential tumour-killing activity of RYBP has made it a promising target for cancer therapy (Novak & Phillips 2008).…”

Section: Discussionmentioning

confidence: 99%

High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids

Andersson¹,

Swärd²,

Stenman³

et al. 2009

Endocrine-Related Cancer

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Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7

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Section: Discussionmentioning

confidence: 99%

High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids

Andersson¹,

Swärd²,

Stenman³

et al. 2009

Endocrine-Related Cancer

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“…However, high levels of dRYBP expression induce apoptosis in all the imaginal discs studied (Figure 1). In transfection experiments, murine and human RYBP/DEDAF proteins have been shown to have the ability to specifically kill mammalian tumor cells while leaving normal cells unaffected [19,20]. We have shown that the induction of apoptosis in Drosophila does not require the apoptotic cell to be in the transformed state, indicating that this may be a useful system to study the mechanisms controlling the tumor-specific cell killing.…”

Section: High Levels Of Exogenous Drybp Induce Apoptosismentioning

confidence: 92%

“…In mammals, high levels of the RYBP protein have been found to have tumor-specific killing activity, a characteristic that could potentially be exploited to develop anti-cancer treatments [19]. Furthermore, the RYBP protein has been found to interact with Apoptin, a protein known to be active in killing tumor cells [20].…”

Section: Introductionmentioning

confidence: 99%

High levels of dRYBP induce apoptosis in Drosophila imaginal cells through the activation of reaper and the requirement of trithorax, dredd and dFADD

González

Busturia

2009

Cell Res

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Drosophila RYBP (dRYBP; Ring1 and YY1 Binding Protein) is a Polycomb and trithorax interacting protein, whose homologous RYBP/DEDAF mammalian counterparts exhibit tumor cell-specific killing activity. Here we show that although endogenous dRYBP is not involved in developmental apoptosis, high levels of exogenous dRYBP induce apoptosis in all the imaginal discs of the fly, indicating that dRYBP apoptotic activity is not specific to tumor cells. We also show that dRYBP-induced apoptosis is inhibited by high levels of either p35 or DIAP1 (Drosophila Inhibitor of Apoptosis Protein 1), and requires the function of the pro-apoptotic REAPER, HID and GRIM proteins, the apical caspase DREDD, the adaptor dFADD protein as well as TRITHORAX (TRX), an epigenetic transcriptional regulator. Furthermore, we demonstrate that overexpression of TRX also induces apoptosis in the imaginal discs. Finally, we show that the expression of reaper-lacZ is upregulated both upon dRYBP-induced apoptosis and upon TRXinduced apoptosis in imaginal discs and that the reaper gene is a direct target of dRYBP in Drosophila embryos. Our results indicate that dRYBP triggers in a receptor-mediated apoptotic pathway that also includes TRX-dependent epigenetic regulation of gene expression.

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“…The functional importance of deleted RYBP in ileal carcinoids still remains to be determined. However, targeting of cancer cells by adenoviral-mediated RYBP expression induces tumor cell-specific apoptosis [77]. Collectively, these data suggest that targeting of RYBP may be a treatment option in a proportion of ileal carcinoids.…”

Section: Genomic Profiling Of Ileal Carcinoidsmentioning

confidence: 97%

Profiling of Ileal Carcinoids

Nilsson

2012

Neuroendocrinology

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Identification of common molecular mechanisms is needed to facilitate the development of new treatment options for patients with ileal carcinoids. Purpose of Review: Recent profiling studies on ileal carcinoids were examined to obtain a comprehensive view of risk factors, genetic aberrations, and transcriptional alterations. Special attention was paid to mechanisms that could provide novel targets for therapy. Results: Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) at IL12A and DAD1 are associated with an increased risk of ileal carcinoids. Genomic profiling revealed distinct patterns of copy-number alterations in ileal carcinoids. Two groups of carcinoids could be identified by hierarchical clustering. A major group of tumors was characterized by loss on chromosome 18 followed by additional losses on chromosomes 3p, 11q, and 13. Three minimal common regions of deletions were identified at 18q21.1–q21.31, 18q22.1–q22.2, and 18q22.3–q23. A minor group of tumors was characterized by clustered gains on chromosomes 4, 5, 7, 14, and 20. Expression profiling identified three groups of ileal carcinoids by principal component analysis. Tumor progression was associated with changes in gene expression including downregulation of MIR133A. Candidate genes for targeted therapy included ERBB2/HER2, DAD1, PRKCA, RYBP, CASP1, CASP4, CASP5, VMAT1, RET, APLP1, OR51E1, GPR112, SPOCK1, RUNX1, and MIR133A.Conclusion: Profiling of ileal carcinoids has revealed recurrent genetic alterations and distinct patterns of gene expression. Frequent alterations in cellular pathways and genes were identified, suggesting novel targets for therapy. Translational studies are needed to validate suggested molecular targets.

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Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis

Cited by 27 publications

References 28 publications

High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids

High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids

High levels of dRYBP induce apoptosis in Drosophila imaginal cells through the activation of reaper and the requirement of trithorax, dredd and dFADD

Profiling of Ileal Carcinoids

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