BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

Gu, Lei; Frommel, Sandra C.; Oakes, Christopher C.; Simon, Ronald; Grupp, Katharina; Gerig, Cristina Yasoma; Bär, Dominik; Robinson, Mark D.; Baer, Constance; Weiß, Melanie; Gu, Zuguang; Schapira, Matthieu; Kuner, Ruprecht; Sültmann, Holger; Provenzano, Maurizio; Yaspo, Marie–Laure; Brors, Benedikt; Korbel, Jan O.; Schlomm, Thorsten; Sauter, Guido; Eils, Roland; Plass, Christoph; Santoro, Raffaella

doi:10.1038/ng.3165

Cited by 142 publications

(159 citation statements)

References 67 publications

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“…Being a key member of the Drosophila Polycomb group (PcG), EZH2 plays a crucial role in gene expression regulation, maintenance of cell identity, stem cell renewal and oncogenesis. Recent studies have shown that EZH2 overexpression predicts poor patient prognosis and is a frequent event in various cancers, such as breast cancer [1], malignant prostate cancer [2], and hepatocellular carcinoma [3]. There are reports depicting the expression and oncogenic role of EZH2 in lung tumorigenesis [4,5] and EZH2 has been suggested to modulate several pathophysiological processes by promoting cell proliferation and cell cycle progression [6], accelerating cell infiltration and metastasis [7], and inhibiting apoptosis [8].…”

Section: Introductionmentioning

confidence: 99%

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Geng¹,

Li²,

Zhou³

et al. 2015

Cancer Letters

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Section: Introductionmentioning

confidence: 99%

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Geng¹,

Li²,

Zhou³

et al. 2015

Cancer Letters

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“…After tumor cells escape the primary site, the epigenome is subjected to microenvironmental signal modulation, conferring cellular plasticity and adaptability to new and inhospitable conditions (Seftor et al 2006;Hendrix et al 2007;Tam and Weinberg 2013). Indeed, multiple studies have unveiled evidence of specific epigenetic pathways involved in the metastatic progression of different cancer types (Cunha et al 2014;Gu et al 2015;Okada et al 2015;Tang et al 2015). Therefore, the combination of genetic and epigenetic events during the course of metastasis likely determines the acquisition of MIC traits.…”

Section: G464vmentioning

confidence: 99%

Distinctive properties of metastasis-initiating cells

2016

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Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies.

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“…(for review, see McStay and Grummt 2008). Interestingly, TIP5 (also known as BAZ2A) is overexpressed in prostate cancer and is involved in maintaining prostate cancer cell growth by directly interacting with EZH2 to maintain epigenetic silencing at Pol II transcribed genes repressed in metastasis (Gu et al 2015). This is a somewhat paradoxical result, since up-regulation of ribosome biogenesis is a feature of most cancers.…”

Section: The Pol I Transcription Machinerymentioning

confidence: 99%

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

2016

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Nucleoli form around tandem arrays of a ribosomal gene repeat, termed nucleolar organizer regions (NORs). During metaphase, active NORs adopt a characteristic undercondensed morphology. Recent evidence indicates that the HMG-box-containing DNA-binding protein UBF (upstream binding factor) is directly responsible for this morphology and provides a mitotic bookmark to ensure rapid nucleolar formation beginning in telophase in human cells. This is likely to be a widely employed strategy, as UBF is present throughout metazoans. In higher eukaryotes, NORs are typically located within regions of chromosomes that form perinucleolar heterochromatin during interphase. Typically, the genomic architecture of NORs and the chromosomal regions within which they lie is very poorly described, yet recent evidence points to a role for context in their function. In Arabidopsis, NOR silencing appears to be controlled by sequences outside the rDNA (ribosomal DNA) array. Translocations reveal a role for context in the expression of the NOR on the X chromosome in Drosophila. Recent work has begun on characterizing the genomic architecture of human NORs. A role for distal sequences located in perinucleolar heterochromatin has been inferred, as they exhibit a complex transcriptionally active chromatin structure. Links between rDNA genomic stability and aging in Saccharomyces cerevisiae are now well established, and indications are emerging that this is important in aging and replicative senescence in higher eukaryotes. This, combined with the fact that rDNA arrays are recombinational hot spots in cancer cells, has focused attention on DNA damage responses in NORs. The introduction of DNA double-strand breaks into rDNA arrays leads to a dramatic reorganization of nucleolar structure. Damaged rDNA repeats move from the nucleolar interior to form caps at the nucleolar periphery, presumably to facilitate repair, suggesting that the chromosomal context of human NORs contributes to their genomic stability. The inclusion of NORs and their surrounding chromosomal environments in future genome drafts now becomes a priority.The relationship between nucleolar organizer regions (NORs) and nucleoli was first established in the 1930s (Heitz 1931;McClintock 1934), but, for decades, the content of the former and the role of the latter remained mysterious. The era of molecular and cellular biology revealed that NORs contain tandem arrays of ribosomal gene (rDNA) repeats and that nucleoli are the sites of ribosome biogenesis. Biochemistry has revealed the inner workings of the nucleolus and the complexity of ribosome biogenesis (for review, see Pederson 2010). However, the genomic architecture of NORs and the chromosomal context in which they lie remains undetermined for most eukaryotes. The resulting void has placed limitations on our understanding of the fundamental mechanisms by which NORs orchestrate formation of the largest structure in the nucleus. In this review, I discuss recent findings regarding the morphology of active NORs and how they seed r...

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BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

Cited by 142 publications

References 67 publications

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Distinctive properties of metastasis-initiating cells

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

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