Emerging functions of C/EBPβ in breast cancer

Matherne, Megan G.; Phillips, Emily S.; Embrey, Samuel J.; Burke, Caitlin M.; Machado, Heather L.

doi:10.3389/fonc.2023.1111522

Cited by 11 publications

(5 citation statements)

References 117 publications

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“…Using a cytokine/chemokine array, we detected an elevated level of IFNβ in 2208L tumors treated with IACS-70654 as compared to controls treated with vehicle ( Figure 5E ). IACS-70654 also downregulated genes involved in the regulation of inflammation and inhibition of cytokine production, such as Cd200 and Cebpb which have been shown to induce immunosuppression in the TIME (Choe and Choi, 2023, Matherne et al, 2023) ( Figure 5A and Supplemental S5C). In tumor cells, these results showed that in 2208L tumor cells IACS-70654 induced both MHCI expression and an IFN response, suggesting induced antigen presentation and immune stimulation including T-cell activation.…”

Section: Resultsmentioning

confidence: 99%

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC

Yuan,

Hao,

Chan

et al. 2024

Preprint

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Tumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.

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Section: Resultsmentioning

confidence: 99%

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC

Yuan,

Hao,

Chan

et al. 2024

Preprint

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“…Gene ontology analysis of these genes showed that 23 of them encode DNA-binding proteins, particularly enriched with zinc-finger TFs (see Additional file 1 : Table S6). A number of these, such as CEBPB, ZNF117 and ZNF92, have been previously proposed as breast cancer markers [ 41 – 43 ] and ZNF273 and ZNF727 have been reported as breast cancer hub genes [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Nucleosome reorganisation in breast cancer tissues

Jacob,

Guiblet,

Mamayusupova

et al. 2024

Clin Epigenet

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Background Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. Results We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5–10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X. Conclusions Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.

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“…Remarkably, these pathways are well-described as oncogenic in specific contexts, predominantly c-JUN [25], IL-6/JAK/STAT3 [26], and TGFβ [27]. C/EBPβ seems to exert an isoform-specific oncogenic role in breast cancer [28]. However, in certain malignancies, these molecules can exert anti-tumor properties in a context-dependent and tumor-stage-dependent manner as well.…”

Section: Discussionmentioning

confidence: 99%

“…C/EBPβ seems to exert an isoform-specific oncogenic role in breast cancer (32). However, in certain malignancies, these molecules can exert anti-tumor properties in a context-dependent and tumor stage-dependent manner as well.…”

Section: Initiation Of Hnscc Differentiation Activates Wound-healing-...mentioning

confidence: 99%

Inducible mucosa-like differentiation of head and neck cancer cells drives the epigenetically determined loss of cell malignancy

Oppel,

Gendreizig,

Martinez-Ruiz

et al. 2023

Preprint

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Head and neck squamous cell carcinomas harbor areas of differentiated tissue known as keratin pearls. Using defined cell culture conditions, we modeled this terminal differentiation by cornification in a primary tumor spheroid model leading to increased cell adhesion, proliferation stop, and diminished tumor-initiating potential. RNA-seq, ATAC-seq, and proteome analysis revealed chromatin closure and a wound healing-associated signaling program via STAT3, SMAD2/3, C/EBPβ, c-JUN and other effectors associated with increased expression of KRT17 and cornification markers including SPRR3. Although KRT17 represents a basal stem-cell marker in normal mucosa, we confirm KRT17 as differentiation marker in human HNSCC tissue. Moreover, we describe a common tissue architecture in normal mucosa and HNSCC tissue with distinct cell differentiation states transitioning from a proliferating basal-like compartment to a wound healing-associated signaling zone to a cornifying core. Thus, our data indicate that the targeted differentiation of HNSCC cells may be a promising strategy for anti-HNSCC therapy.

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Emerging functions of C/EBPβ in breast cancer

Cited by 11 publications

References 117 publications

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC

CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC

Nucleosome reorganisation in breast cancer tissues

Inducible mucosa-like differentiation of head and neck cancer cells drives the epigenetically determined loss of cell malignancy

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