Solid tumours hijack the histone variant network

Ghiraldini, Flávia Gerelli; Filipescu, Dan; Bernstein, Emily

doi:10.1038/s41568-020-00330-0

Cited by 51 publications

(44 citation statements)

References 300 publications

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“…In breast cancer, the mRNA expression of the histone variant H2A.Z correlates with the mRNA levels of cell cycle proteins, including cyclins ( 204 ). H2A.Z may be of particular importance for ERα-driven breast cancer ( 203 ). Of the two H2A.Z proteins, H2A.Z.1 and H2A.Z.2, H2A.Z.1 is regulated by ERα through an ERE site in its gene h2afz .…”

Section: Chromatin Accessibilitymentioning

confidence: 99%

“…Non-Canonical Histone Variant H2A.Z Histone variants replace canonical histones at certain places of the chromatin, particularly in transcriptionally active regions of the genome, and thereby locally influence epigenetics (203). Histone variants may allow higher rates of nucleosome turnover and may improve chromatin remodeling at active promoters and enhancers.…”

Section: Hdacsmentioning

confidence: 99%

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Nuclear Mechanisms Involved in Endocrine Resistance

Dittmer

2021

Front. Oncol.

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Endocrine therapy is a standard treatment offered to patients with ERα (estrogen receptor α)-positive breast cancer. In endocrine therapy, ERα is either directly targeted by anti-estrogens or indirectly by aromatase inhibitors which cause estrogen deficiency. Resistance to these drugs (endocrine resistance) compromises the efficiency of this treatment and requires additional measures. Endocrine resistance is often caused by deregulation of the PI3K/AKT/mTOR pathway and/or cyclin-dependent kinase 4 and 6 activities allowing inhibitors of these factors to be used clinically to counteract endocrine resistance. The nuclear mechanisms involved in endocrine resistance are beginning to emerge. Exploring these mechanisms may reveal additional druggable targets, which could help to further improve patients’ outcome in an endocrine resistance setting. This review intends to summarize our current knowledge on the nuclear mechanisms linked to endocrine resistance.

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Section: Chromatin Accessibilitymentioning

confidence: 99%

Section: Hdacsmentioning

confidence: 99%

Nuclear Mechanisms Involved in Endocrine Resistance

Dittmer

2021

Front. Oncol.

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“…The role of H2A.Z in disease has been extensively studied, particularly in cancer. In 2002, H2A.Z overexpression was demonstrated in colorectal cancer [136] and, since then, there has been an increasing number of publications reporting a pro-oncogenic role of H2A.Z [137,138]. H2A.Z has also been involved in other diseases beyond cancer [53].…”

Section: Highlightsmentioning

confidence: 99%

The H2A.Z-nucleosome code in mammals: emerging functions

2022

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H2A.Z is a histone variant that provides specific structural and docking-side properties to the nucleosome, resulting in diverse and specialised molecular and cellular functions. In this review, we discuss the latest studies uncovering new functional aspects of mammalian H2A.Z in gene transcription, including pausing and elongation of RNA polymerase II (RNAPII) and enhancer activity; DNA repair; DNA replication; and 3D chromatin structure. We also review the recently described role of H2A.Z in embryonic development, cell differentiation, neurodevelopment, and brain function. In conclusion, our cumulative knowledge of H2A.Z over the past 40 years, in combination with the implementation of novel molecular technologies, is unravelling an unexpected and complex role of histone variants in gene regulation and disease.

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“…Beyond the biomarker potential, the biological ramifications of this are worthy of consideration. Histone variants and their chaperones are altered in solid tumors and play a fundamental role in compacting DNA into nucleosomes to aid DNA packaging and cellular proliferation [ 50 ]. Based on the premise that EV packaged proteins directly reflects their cell of origin by mimicking expression or action, it is curious that EV associated histones are increased in non-nodal OTSCC yet decreased in nodal disease.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma

Leung

Ngai

et al. 2021

Cells

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Lymph node metastasis is the most reliable indicator of a poor prognosis for patients with oral tongue cancers. Currently, there are no biomarkers to predict whether a cancer will spread in the future if it has not already spread at the time of diagnosis. The aim of this study was to quantitatively profile the proteomes of extracellular vesicles (EVs) isolated from blood samples taken from patients with oral tongue squamous cell carcinoma with and without lymph node involvement and non-cancer controls. EVs were enriched using size exclusion chromatography (SEC) from pooled plasma samples of patients with non-nodal and nodal oral tongue squamous cell carcinoma (OTSCC) and non-cancer controls. Protein cargo was quantitatively profiled using isobaric labelling (iTRAQ) and two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. We identified 208 EV associated proteins and, after filtering, generated a short list of 136 proteins. Over 85% of the EV-associated proteins were associated with the GO cellular compartment term “extracellular exosome”. Comparisons between non-cancer controls and oral tongue squamous cell carcinoma with and without lymph node involvement revealed 43 unique candidate EV-associated proteins with deregulated expression patterns. The shortlisted EV associated proteins described here may be useful discriminatory biomarkers for differentiating OTSCC with and without nodal disease or non-cancer controls.

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Solid tumours hijack the histone variant network

Cited by 51 publications

References 300 publications

Nuclear Mechanisms Involved in Endocrine Resistance

Nuclear Mechanisms Involved in Endocrine Resistance

The H2A.Z-nucleosome code in mammals: emerging functions

Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma

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