The <i>RET</i> oncogene is a critical component of transcriptional programs associated with retinoic acid–induced differentiation in neuroblastoma

Oppenheimer, Orit; Cheung, Nai‐Kong V.; Gerald, William L.

doi:10.1158/1535-7163.mct-06-0587

Cited by 44 publications

(44 citation statements)

References 48 publications

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“…Notably, the most significantly enriched functional categories (P < 0.05) upon CHAF1A silencing are associated with multiple processes involved in neuronal differentiation (axonogenesis, synaptic transmission, cell-cell signaling, catecholamine biosynthesis, and nervous system development; Table 2), validating CHAF1A as a potential critical regulator of neuronal differentiation. Furthermore, these functional categories were distinct from the ones described to be enriched in neuroblastoma-cell differentiation upon Cyclin D1 and Cdk4 silencing (29) or retinoic acid treatment (30), suggesting a distinctive mechanism for CHAF1A in inducing cell differentiation (Supplementary Tables S1 and S2). In addition, GSEA revealed that genes regulated by CHAF1A were associated with major metabolic and oncogenic pathways.…”

Section: Chaf1a Silencing Induces Neuronal Differentiation Pathways Amentioning

confidence: 94%

Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma

et al. 2014

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Neuroblastoma arises from the embryonal neural crest secondary to a block in differentiation. Long-term patient survival correlates inversely with the extent of differentiation, and treatment with retinoic acid or other prodifferentiation agents improves survival modestly. In this study, we show the histone chaperone and epigenetic regulator CHAF1A functions in maintaining the highly dedifferentiated state of this aggressive malignancy. CHAF1A is a subunit of the chromatin modifier chromatin assembly factor 1 and it regulates H3K9 trimethylation of key target genes regulating proliferation, survival, and differentiation. Elevated CHAF1A expression strongly correlated with poor prognosis. Conversely, CHAF1A loss-of-function was sufficient to drive neuronal differentiation in vitro and in vivo. Transcriptome analysis of cells lacking CHAF1A revealed repression of oncogenic signaling pathways and a normalization of glycolytic metabolism. Our findings demonstrate that CHAF1A restricts neural crest differentiation and contributes to the pathogenesis of high-risk neuroblastoma. Cancer Res; 74(3); 765-74. Ó2013 AACR.

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Section: Chaf1a Silencing Induces Neuronal Differentiation Pathways Amentioning

confidence: 94%

Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma

et al. 2014

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“…Studies have demonstrated that RET is required for retinoic acid-induced neuroblastoma differentiation [158], and that RET inhibition is effective in neuroblastoma preclinical models [159]. Other recent studies have identified the polo-like kinase 1 (PLK1) as a potential target for neuroblastoma therapy, based on screens of a library of kinase inhibitors in neuroblastoma preclinical models [160], while a screening study using an siRNA library identified the checkpoint kinase 1 (CHK1) as a potential target [161].…”

Section: Treatment -Relapsed and Refractory Neuroblastomamentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

311

258

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Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

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“…It is considered to be an embryonic tumor arising from immature cells of the neural crest, probably due to genetic and molecular alterations that result in arrested cell differentiation and uncontrolled proliferation. In general, neuroblastic tumors are characterized by extreme clinical and pathological heterogeneity (32). The induced differentiation of tumor cells is regarded to be therapeutically advantageous, since more extensively differentiated neuroblastic tumors are usually associated with lower stage and better clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

“…The induced differentiation of tumor cells is regarded to be therapeutically advantageous, since more extensively differentiated neuroblastic tumors are usually associated with lower stage and better clinical outcome. Therefore, differentiating agents such as retinoic acid, which is known to induce differentiation in several tumor types including neuroblastoma, have become a part of the therapeutic arsenal (10)(11)(12)20,32).…”

Section: Discussionmentioning

confidence: 99%

“…The biological effects of RA and retinoids are generally mediated by inducible nuclear retinoid receptors (RARs and RXRs), which regulate transcription of genes with RA- responsive elements (32,33). The cellular retinol-binding proteins (CRBP) and cytoplasmic retinoic acid-binding proteins (CRABP-1 and CRABP-2) enhance the binding of RA to their respective receptors (34).…”

Section: Discussionmentioning

confidence: 99%

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Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

Rédová

Chlapek²,

Loja³

et al. 2009

Int J Mol Med

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Abstract.We investigated the possible modulation by LOX/ COX inhibitors of all-trans retinoic acid (ATRA)-induced cell differentiation in two established neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Caffeic acid, as an inhibitor of 5-lipoxygenase, and celecoxib, as an inhibitor of cyclooxygenase-2, were chosen for this study. The effects of the combined treatment with ATRA and LOX/COX inhibitors on neuroblastoma cells were studied using cell morphology assessment, detection of differentiation markers by immunoblotting, measurement of proliferation activity, and cell cycle analysis and apoptosis detection by flow cytometry. The results clearly demonstrated the potential of caffeic acid to enhance ATRA-induced cell differentiation, especially in the SK-N-BE(2) cell line, whereas application of celecoxib alone or with ATRA led predominantly to cytotoxic effects in both cell lines. Moreover, the higher sensitivity of the SK-N-BE(2) cell line to combined treatment with ATRA and LOX/COX inhibitors suggests that cancer stem cells are a main target for this therapeutic approach. Nevertheless, further detailed study of the phenomenon of enhanced cell differentiation by expression profiling is needed.

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The RET oncogene is a critical component of transcriptional programs associated with retinoic acid–induced differentiation in neuroblastoma

Abstract: Differentiation is a key feature in pathologic classification and prognosis of neuroblastic tumors, although the underlying molecular mechanisms are not well defined. To identify key differentiation-related molecules and path-

Cited by 44 publications

References 48 publications

Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma

Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma

Overview and recent advances in the treatment of neuroblastoma

Influence of LOX/COX inhibitors on cell differentiation induced by all-trans retinoic acid in neuroblastoma cell lines

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