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The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma [ChIP-seq]

ABSTRACT: Mapping the genome-wide binding profile of ETS1 in a Mesenchymal HNSCC Cell Line using ChIP-Seq techniques

ORGANISM(S): Homo sapiens

PROVIDER: GSE109884 | GEO | 2019/07/08

REPOSITORIES: GEO

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The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma [RNA-seq knock-down]

Project description:RNA-Sequencing Analysis of gene expression changes due to ablation of Ets1 in SCC25 Cells.

2019-07-08 | GSE109886 | GEO

Molecular dissection of the oncogenic role of ETS1 in the mesenchymal subtypes of head and neck squamous cell carcinoma.

Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous disease of significant mortality and with limited treatment options. Recent genomic analysis of HNSCC tumors has identified several distinct molecular classes, of which the mesenchymal subtype is associated with Epithelial to Mesenchymal Transition (EMT) and shown to correlate with poor survival and drug resistance. Here, we utilize an integrated approach to characterize the molecular function of ETS1, an oncogenic transcription factor specifically enriched in Mesenchymal tumors. To identify the global ETS1 cistrome, we have performed integrated analysis of RNA-Seq, ChIP-Seq and epigenomic datasets in SCC25, a representative ETS1high mesenchymal HNSCC cell line. Our studies implicate ETS1 as a crucial regulator of broader oncogenic processes and specifically Mesenchymal phenotypes, such as EMT and cellular invasion. We found that ETS1 preferentially binds cancer specific regulator elements, in particular Super-Enhancers of key EMT genes, highlighting its role as a master regulator. Finally, we show evidence that ETS1 plays a crucial role in regulating the TGF-β pathway in Mesenchymal cell lines and in leading-edge cells in primary HNSCC tumors that are endowed with partial-EMT features. Collectively our study highlights ETS1 as a key regulator of TGF-β associated EMT and reveals new avenues for sub-type specific therapeutic intervention.

| S-EPMC6657958 | biostudies-literature

MicroRNA-based subtypes in head and neck squamous cell carcinoma

Project description:Highly coordinated, deregulated expressions of microRNAs (miRNA) have been implicated in the development of various cancers, including head and neck squamous cell carcinoma (HNSCC). Outside of HPV infection, molecular classification of HNSCC is lacking, and patient stratification by anatomical location and stage does not account for the heterogenous clinical courses seen. Previous studies have proposed molecular classifications based on gene expression, but none describe the role of microRNA expression in HNSCC subtyping. In this study, we identified reliable miRNA clusters that can be used to subclassify HNSCC tumors as well as other squamous tumors of other anatomic locations. An institutional discovery cohort was generated using miRNA expression data from microarrays, and this was validated using publicly available next-generation microRNA sequencing data from TCGA. Further analysis of these subtypes revealed distinct biological and clinical features of HNSCC tumors based on the miRNA expression profiles, which provides new insights into the pathogenesis and treatment of HNSCC.

2020-04-01 | GSE144711 | GEO

The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-08 | GSE109896 | GEO

Molecular Subtypes in Head and Neck Cancer [expression]

2013-03-01 | GSE39366 | GEO

Molecular Subtypes in Head and Neck Cancer [expression]

Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease whose underlying etiology has not been explained by traditional prognostic factors such as tumor site, stage, or histology. Although previous studies have shown that molecular subtypes of HNSCC exist, the benefit of such a classification scheme has not been fully realized. We show that molecular subtypes of HNSCC exist; that these subtypes have distinct patterns of chromosomal gain and loss, some of which affect canonical oncogenes and tumor suppressors; and that the subtypes are biologically and clinically relevant. These subtypes provide new insight into HNSCC etiology, as well as a valuable method for classifying HNSCC tumors. A total of 163 samples were considered. Quality control procedures were applied to microarray probe-level intensity files. A total of 138 tumor arrays remained after removing low-quality arrays, duplicate arrays, and arrays from non-HNSCC samples. The normexp background correction and loess normalization procedures were applied to the probe-level data. After log transformation, probes were matched to a common gene database to produce expression values for 15595 genes.

2013-03-01 | E-GEOD-39366 | biostudies-arrayexpress

DYRK1A, a potential therapeutic target for head and neck squamous cell carcinoma

Project description:To identify the activated tyrosine kinase signaling pathways in HNSCC, we carried out phosphotyrosine profiling using a panel of HNSCC cell lines compared to a normal oral keratinocyte. A total of 61 unique phosphosites were identified across these cell lines. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Y321 in all the HNSCC cell lines compared to the normal oral cell line OKF6/TERT1. Inhibition of DYRK1A using its specific siRNA and inhibitor resulted in a decrease in the invasion and colony formation ability of the HNSCC cell lines. Further, the treatment of mice bearing HNSCC xenograft tumors with DYRK1A inhibitor (harmine) showed regression of tumor growth. Our results demonstrate that DYRK1A could be a novel therapeutic target in HNSCC.

2018-10-24 | PXD002132 | Pride

The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma

Project description:The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma

| PRJNA432255 | ENA

Molecular Subtypes in Head and Neck Cancer [copy number]

2013-03-01 | GSE39367 | GEO

The Molecular Dissection of the Oncogenic Role of ETS1 in the Mesenchymal Subtypes of Head and Neck Squamous Cell Carcinoma [RNA-seq Cell lines]

Project description:RNA-Sequencing Analysis was performed on 7 Head and Neck Squamous Cell Carcinoma Cells Lines in order to examine their overall gene expression profiles.

2019-07-08 | GSE109885 | GEO

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