Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate Cancer

Zou, June X.; Guo, Linlang; Revenko, Alexey S.; Tepper, Clifford G.; Gemo, Abigael T.; Kung, Hsing Jien; Chen, Hong Wu

doi:10.1158/0008-5472.can-08-3440

Cited by 140 publications

(170 citation statements)

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“…In the absence of such specific regulation of the N-terminal domain, Atad2-L/ATAD2 may act as a boundary as does the yeast Atad2 ortholog, Yta7, although presenting a non-functional bromodomain (Jambunathan et al, 2005;Gradolatto et al, 2008). This activity of ATAD2 could also explain the chromatin 'freezing' property of the protein revealed here, in addition to its role as a co-activator in specific regulatory pathways recently described (Zou et al, 2007(Zou et al, , 2009Ciro et al, 2009).…”

Section: Atad2: a New Epigenome Regulatormentioning

confidence: 57%

“…This correlation was not, however, confirmed in the case of lymphoma, suggesting that ATAD2 may cooperate with cell type-specific factors to induce an aggressive behavior of the cells, a hypothesis which is in agreement with its demonstrated involvement in the estrogen and androgen receptor pathways and its activity as an MYC co-factor (Zou et al, 2007(Zou et al, , 2009Ciro et al, 2009).…”

Section: Atad2: a New Epigenome Regulatormentioning

confidence: 87%

“…In addition, a genetic screen in Caenorabditis elegans suggests its involvement in the silencing of repeated transgenes (Tseng et al, 2007). Interestingly, recently several laboratories have reported the overexpression of human ATAD2 in different cancer types, and have attempted to understand its potential contribution to oncogenesis (Zou et al, 2007(Zou et al, , 2009Ciro et al, 2009). One of these studies shows that human ATAD2 is a target of estrogen in human breast cancer cells, and controls the estrogen-dependent expression of several ER-a target genes (Zou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…One of these studies shows that human ATAD2 is a target of estrogen in human breast cancer cells, and controls the estrogen-dependent expression of several ER-a target genes (Zou et al, 2007). Another study reveals its action as an androgen-receptor coactivator, overexpressed in hormone-independent prostate cancer cell lines as well as in a subset of prostate cancers (Zou et al, 2009). All these investigations also highlighted the activity of ATAD2 as a transcriptional regulator, which, in addition to the estrogen and androgen receptors pathways, functions as a MYC cofactor (Ciro et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

et al. 2010

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Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation.

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Section: Atad2: a New Epigenome Regulatormentioning

confidence: 57%

Section: Atad2: a New Epigenome Regulatormentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

et al. 2010

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“…ATAD2 contained two AAA (ATPases Associated with diverse cellular Activities) domains, and was identified as an AR (androgen receptor) coactivator . ATAD2 is directly regulated by protooncogenes like ACTR, AIB1 and SRC-3, and is highly expressed in prostate cancer cells as a critical factor for prostate cancer cell proliferation and survival (Zou et al, 2007;Zou et al, 2009). Moreover, ATAD2 can regulate downstream genes such as cyclin D1, c-Myc, and E2F1, which contributed directly or indirectly to cell proliferation .…”

Section: Atad2 Is Highly Expressed In Ovarian Carcinomas and Indicatementioning

confidence: 99%

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Wan¹,

Zhang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The purpose of this study was to explore the expression of ATAD2 in ovarian tumor tissue as well as its relationship with degree of malignancy. Tumor tissue from 110 cases of ovarian cancer was collected in accordance with the Declaration of Helsinki for evaluation of ATAD2 expression iimmunohistochemistry, quantitative PCR (qPCR) and Western blotting. The correlation between the ATAD2 expression and and the prognosis of ovarian cancer was evaluated by Cox regression model. In addition, HO-8910 and OVCAR-3 cells were transfected with two siRNAs targeting ATAD2. Cell viability was evaluated with MTT assay, and cell migration by transwell migration assay. ATAD2 was shown to be highly expressed in 65.5% (72/110) of ovarian cancer cases, both at transcriptional and protein levels. Moreover, highly expression was positively correlated with degree of malignancy. Knock-down of ATAD2 in HO-8910 and OVCAR-3 cells was found to reduce cell migration. In addition, follow-up visits of the patients demonstrated that the 5-year survival rate was lower in patients with high expression of ATAD2. Our study suggested that ovarian tumor tissue may have highly expressed ATAD2, which is associated with tumor stage, omentum-metastasis, ascites and CA-125. Increased ATAD2 may play important roles in tumor proliferation and migration. ATAD2 could serve in particular as a prognostic marker and a therapeutic target for ovarian cancer.

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A Chemical Probe for the ATAD2 Bromodomain

et al. 2016

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ATAD2 is a cancer‐associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio‐isostere to exploit the unique properties of fluorine, and 2) using 1,3‐interactions to control the conformation of a piperidine ring. This resulted in the first reported low‐nanomolar, selective and cell permeable chemical probe for ATAD2.

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Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate Cancer

Cited by 140 publications

References 42 publications

Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

A Chemical Probe for the ATAD2 Bromodomain

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