Histone variants: critical determinants in tumour heterogeneity

Wang, Tao; Chuffart, Florent; Bourova-Flin, Ekaterina; Wang, Jin; Mi, Jian-Qing; Rousseaux, Sophie; Khochbin, Saadi

doi:10.1007/s11684-018-0667-3

Cited by 16 publications

(8 citation statements)

References 58 publications

(85 reference statements)

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“…These processes are most likely upregulated in tissue remodelling following radiation treatment [ 33 , 34 ]. The linker histone H1 is of particular interest as it also seems to be implicated in diseases such as cancer [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients

Hynne

Aqrawi

Jensen

et al. 2022

IJMS

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Patients with head and neck cancer (HNC) and patients with primary Sjögren’s syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients

Hynne

Aqrawi

Jensen

et al. 2022

IJMS

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“…Furthermore, H2B1O and H2B1D were identified to be upregulated in WaGa, and H2B1C, H2B1K, H2B2F and H2AJ in MCC13. The role of histone variants in the development of carcinomas has been discussed and described in a number of publications [39–46]. As described in a recent review, canonical histones can be replaced with variant histones after environmental-stress-induced DNA damage repair, which subsequently results in a change in chromatin structure and stability [47].…”

Section: Resultsmentioning

confidence: 99%

Quantitative proteome analysis of Merkel cell carcinoma cell lines using SILAC

Kotowski

Erović²,

Schnoell

et al. 2019

Clin Proteom

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BackgroundMerkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin with growing incidence. To better understand the biology of this malignant disease, immortalized cell lines are used in research for in vitro experiments. However, a comprehensive quantitative proteome analysis of these cell lines has not been performed so far.MethodsStable isotope labelling by amino acids in cell culture (SILAC) was applied to six MCC cell lines (BroLi, MKL-1, MKL-2, PeTa, WaGa, and MCC13). Following tryptic digest of labelled proteins, peptides were analysed by mass spectrometry. Proteome patterns of MCC cell lines were compared to the proteome profile of an immortalized keratinocyte cell line (HaCaT).ResultsIn total, 142 proteins were upregulated and 43 proteins were downregulated. Altered proteins included mitoferrin-1, histone H2A type 1-H, protein-arginine deiminase type-6, heterogeneous nuclear ribonucleoproteins A2/B1, protein SLX4IP and clathrin light chain B. Furthermore, several proteins of the histone family and their variants were highly abundant in MCC cell lines.ConclusionsThe results of this study present a new protein map of MCC and provide deeper insights in the biology of MCC. Data are available via ProteomeXchange with identifier PXD008181.

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“…Thus, Table 16 shows a randomly selected list of up-regulated pathways and hence proteins found to be common across 2-5 cell lines. It is noteworthy from the clinical data, i.e., elevated expression of these genes at the primary tumor, was associated with both a poor survival (e.g., Fig 9: FLNB [49] and H1F0 [50] genes) as well as an enhanced or better survival (e.g., CDC42 & HLA-A, lower portion of Table 16). Thus, this analysis indicates that an overexpression of proteins at metastatic sites, relative to primary tumor levels as well as, from the clinical data, relative to normal breast tissue levels rather than normal tissue of origin levels can complicate/ contradict the interpretation of disease free survival.…”

Section: Plos Onementioning

confidence: 97%

Divergent organ-specific isogenic metastatic cell lines identified using multi-omics exhibit differential drug sensitivity

et al. 2020

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Background Monitoring and treating metastatic progression remains a formidable task due, in part, to an inability to monitor specific differential molecular adaptations that allow the cancer to thrive within different tissue types. Hence, to develop optimal treatment strategies for metastatic disease, an important consideration is the divergence of the metastatic cancer growing in visceral organs from the primary tumor. We had previously reported the establishment of isogenic human metastatic breast cancer cell lines that are representative of the common metastatic sites observed in breast cancer patients. Methods Here we have used proteomic, RNAseq, and metabolomic analyses of these isogenic cell lines to systematically identify differences and commonalities in pathway networks and examine the effect on the sensitivity to breast cancer therapeutic agents. Results Proteomic analyses indicated that dissemination of cells from the primary tumor sites to visceral organs resulted in cell lines that adapted to growth at each new site by, in part, acquiring protein pathways characteristic of the organ of growth. RNAseq and metabolomics analyses further confirmed the divergences, which resulted in differential efficacies to commonly used FDA approved chemotherapeutic drugs. This model system has provided data that indicates that organ-specific growth of malignant lesions is a selective adaptation and growth process. Conclusions The insights provided by these analyses indicate that the rationale of targeted treatment of metastatic disease may benefit from a consideration that the biology of metastases has diverged from the primary tumor biology and using primary tumor traits as the basis for treatment may not be ideal to design treatment strategies.

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Histone variants: critical determinants in tumour heterogeneity

Cited by 16 publications

References 58 publications

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients

Quantitative proteome analysis of Merkel cell carcinoma cell lines using SILAC

Divergent organ-specific isogenic metastatic cell lines identified using multi-omics exhibit differential drug sensitivity

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