Quantifying Tip60 (Kat5) stratifies breast cancer

McGuire, Andrew; Casey, Máire‐Caitlín; Shalaby, A. M.; Kalinina, Olga; Curran, Catherine; Webber, Mark; Callagy, Grace; Bourke, Emer; Kerin, Michael J.; Brown, James A. L.

doi:10.1038/s41598-019-40221-5

Cited by 20 publications

(13 citation statements)

References 41 publications

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“…As previously described [35], the prognostic value of Ago2 mRNA expression was investigated using Breast Cancer database of The Kaplan-Meier Plotter (incorporating gene expression and clinical data) (http://kmplot.com/analysis/) [16–19]. At use, data on 5143 breast cancer patients was available (December 2017).…”

Section: Methodsmentioning

confidence: 99%

“…At use, data on 5143 breast cancer patients was available (December 2017). Specific parameters used as previously described [35]: Gene: EIF2C2 (Search: AGO2) (Affy ID: 225827_at); Split patients by: median; Survival: Disease Free Survival (DFS n = 1402) or Overall Survival (OS, n = 626); Follow up threshold: all; Censure at threshold, selected; Use only JetSet best probe set, selected; Quality control, Remove redundant samples: checked; Array quality control: exclude biased arrays selected; Intrinsic subtype, selected as indicated.…”

Section: Methodsmentioning

confidence: 99%

“…As previously described [35], somatic mutations and copy number changes to the Ago2 gene were investigated using the cBioPortal database [The Cancer Genome Atlas, Breast Cancer dataset] (http://www.cbioportal.org/) [20–24]. Specific Search parameters (as previously described [35]): Select Studies: Breast Cancer; Studies Select all: As of December 2017 9 studies available [Adenoid Cystic Carcinoma of the Breast (MSKCC, J Pathol.…”

Section: Methodsmentioning

confidence: 99%

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Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer

et al. 2019

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Background Argonaute-2 (Ago2) is an essential component of microRNA biogenesis implicated in tumourigenesis. However Ago2 expression and localisation in breast cancer remains undetermined. The aim was to define Ago2 expression (mRNA and protein) and localisation in breast cancer, and investigate associations with clinicopathological details. Methods Ago2 protein was stained in breast cancer cell lines and tissue microarrays (TMAs), with intensity and localization assessed. Staining intensity was correlated with clinicopathological details. Using independent databases, Ago2 mRNA expression and gene alterations in breast cancer were investigated. Results In the breast cancer TMAs, 4 distinct staining intensities were observed (Negative, Weak, Moderate, Strong), with 64.2% of samples stained weak or negatively for Ago2 protein. An association was found between strong Ago2 staining and, the Her2 positive or basal subtypes, and between Ago2 intensity and receptor status (Estrogen or Progesterone). In tumours Ago2 mRNA expression correlated with reduced relapse free survival. Conversely, Ago2 mRNA was expressed significantly lower in SK-BR-3 (HER2 positive) and BT-20 (Basal/Triple negative) cell lines. Interestingly, high levels of Ago2 gene amplification (10–27%) were observed in breast cancer across multiple patient datasets. Importantly, knowledge of Ago2 expression improves predictions of breast cancer subtype by 20%, ER status by 15.7% and PR status by 17.5%. Conclusions Quantification of Ago2 improves the stratification of breast cancer and suggests a differential role for Ago2 in breast cancer subtypes, based on levels and cellular localisation. Further investigation of the mechanisms affecting Ago2 dysregulation will reveal insights into the molecular differences underpinning breast cancer subtypes. Electronic supplementary material The online version of this article (10.1186/s12885-019-5884-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer

et al. 2019

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“…In fact, mutation at this lysine acetylation site hindered the binding of Tip60 to the human NuA4 complex, suppressed the acetyltransferase activity of Tip60 and inhibited the expression of pro-apoptotic genes upon glucose starvation [52]. These studies suggest a protective effect of Tip60 in cancer, and its downregulation in some tumors [79,80] may explain a mechanism by which cancer cells adapt to metabolic stress.…”

Section: Molecular Effects Of Tip60 On Glucose Metabolism and Mitochomentioning

confidence: 89%

“…downregulation in some tumors [79,80] may explain a mechanism by which cancer cells adapt to metabolic stress.…”

Section: Molecular Effects Of Tip60 On Glucose Metabolism and Mitochomentioning

confidence: 99%

Metabolic Roles of Androgen Receptor and Tip60 in Androgen-Dependent Prostate Cancer

Tan

Avery

Carrasco‐Pozo

2020

IJMS

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Androgen receptor (AR)-mediated signaling is essential for the growth and differentiation of the normal prostate and is the primary target for androgen deprivation therapy in prostate cancer. Tat interactive protein 60 kDa (Tip60) is a histone acetyltransferase that is critical for AR activation. It is well known that cancer cells rewire their metabolic pathways in order to sustain aberrant proliferation. Growing evidence demonstrates that the AR and Tip60 modulate key metabolic processes to promote the survival of prostate cancer cells, in addition to their classical roles. AR activation enhances glucose metabolism, including glycolysis, tricarboxylic acid cycle and oxidative phosphorylation, as well as lipid metabolism in prostate cancer. The AR also interacts with other metabolic regulators, including calcium/calmodulin-dependent kinase kinase 2 and mammalian target of rapamycin. Several studies have revealed the roles of Tip60 in determining cell fate indirectly by modulating metabolic regulators, such as c-Myc, hypoxia inducible factor 1α (HIF-1α) and p53 in various cancer types. Furthermore, Tip60 has been shown to regulate the activity of key enzymes in gluconeogenesis and glycolysis directly through acetylation. Overall, both the AR and Tip60 are master metabolic regulators that mediate cellular energy metabolism in prostate cancer, providing a framework for the development of novel therapeutic targets in androgen-dependent prostate cancer.

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Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

Liu

Guo

et al. 2023

MedComm

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Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the “histone code.” The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post‐translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone‐modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

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Quantifying Tip60 (Kat5) stratifies breast cancer

Cited by 20 publications

References 41 publications

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer

Metabolic Roles of Androgen Receptor and Tip60 in Androgen-Dependent Prostate Cancer

Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

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