Bulk RNA-Seq of head and neck squamous cell carcinomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE310041 | GEO | 2025/11/20
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE11929: Identification of a subgroup of head and neck cancers lacking numerical chromosomal aberrations GSE11931: Copy Number Alterations in HNSCC with or without Oncogene Expressing Human Papillomavirus Refer to individual Series
2009-03-11 | E-GEOD-12020 | biostudies-arrayexpress
Project description:Rigosertib treatment of head and neck squamous cell cancer The dual pathway inhibitor rigosertib inhibits phosphoinositide 3-kinase (PI3K) pathway activation as well as polo-like kinase 1 (PLK1) activity across a broad spectrum of cancer cell lines. The importance of PIK3CA alterations in head and neck squamous cell cancer (HNSCC) has raised interest in exploring agents targeting PI3K, the product of PIK3CA. The genetic and molecular basis of rigosertib treatment response was investigated in a panel of 16 HNSCC cell lines, and direct patient tumor xenografts from 8 HNSCC patients (4 HPV16-positive). HNSCC cell lines and xenografts were characterized by pathway enrichment gene expression analysis, exon sequencing, gene copy number, western blotting, and IHC. Rigosertib had potent antiproliferative effects on 11 of the 16 HPV- HNSCC cell lines. Treatment sensitivity was confirmed in two cell lines using an orthotopic in vivo xenograft model. Growth reduction after rigosertib treatment was observed in 3/8 HNSCC direct patient tumor lines. The responsive tumor lines carried a combination of a PI3KCA activating event (amplification or mutation) and a p53 inactivating event (either HPV16-mediated or mutation-mediated TP53 inactivation). In this study, we evaluated the in vitro and in vivo efficacy of rigosertib in both HPV+ and HPV- HNSCCs focusing on inhibition of the PI3K pathway. Although consistent inhibition of the PI3K pathway was not evident in HNSCC, we identified a combination of PI3K/TP53 events necessary, but not sufficient for rigosertib-sensitivity. Sixteen HNSCC lines data were profiled at baseline to find differentially expressed genes and pathways sensitive to rigosertib.
2013-06-13 | E-GEOD-47864 | biostudies-arrayexpress
Project description:Rigosertib treatment of head and neck squamous cell cancer The dual pathway inhibitor rigosertib inhibits phosphoinositide 3-kinase (PI3K) pathway activation as well as polo-like kinase 1 (PLK1) activity across a broad spectrum of cancer cell lines. The importance of PIK3CA alterations in head and neck squamous cell cancer (HNSCC) has raised interest in exploring agents targeting PI3K, the product of PIK3CA. The genetic and molecular basis of rigosertib treatment response was investigated in a panel of 16 HNSCC cell lines, and direct patient tumor xenografts from 8 HNSCC patients (4 HPV16-positive). HNSCC cell lines and xenografts were characterized by pathway enrichment gene expression analysis, exon sequencing, gene copy number, western blotting, and IHC. Rigosertib had potent antiproliferative effects on 11 of the 16 HPV- HNSCC cell lines. Treatment sensitivity was confirmed in two cell lines using an orthotopic in vivo xenograft model. Growth reduction after rigosertib treatment was observed in 3/8 HNSCC direct patient tumor lines. The responsive tumor lines carried a combination of a PI3KCA activating event (amplification or mutation) and a p53 inactivating event (either HPV16-mediated or mutation-mediated TP53 inactivation). In this study, we evaluated the in vitro and in vivo efficacy of rigosertib in both HPV+ and HPV- HNSCCs focusing on inhibition of the PI3K pathway. Although consistent inhibition of the PI3K pathway was not evident in HNSCC, we identified a combination of PI3K/TP53 events necessary, but not sufficient for rigosertib-sensitivity.
2013-06-13 | GSE47864 | GEO
Project description:The conserved Hippo-YAP signaling pathway is involved in homeostasis and organ development through the regulation of cell growth and cell death. Its downstream effectors YAP1, WWTR1 (TAZ), and TEAD are transcriptionally active in the majority of human cancers, often as a result of copy-number variation or inactivating mutations of core components and upstream regulators. Analysis of The Cancer Genome Atlas and other published data of head and neck squamous cell carcinoma (HNSCC) reveals somatic alterations of the Hippo-YAP pathway in approximately 50% of HNSCC, making it the most altered pathway in these cancers. Unfortunately, highly specific inhibitors targeting the YAP1 transcriptional complex are not available, and better strategies to target this pathway are sought. Here, we show that FAT1 (FAT Atypical Cadherin 1), an upstream inhibitor of YAP1, is mutated either by missense or truncating mutation in 29% of HNSCC. Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibit selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.
2023-07-12 | GSE201714 | GEO
Project description:Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G-protein-coupled receptor kinase-2 (GRK2) expression is reduced in undifferentiated, high-grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial-to-mesenchymal transition (EMT) phenotypic features, an EMT-like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC
2019-12-31 | GSE111932 | GEO
Project description:Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and the human papillomavirus (HPVP+P)-driven subtype is the fastest rising in North America. Although most cases of HPV+ HNSCC respond to radiation and chemotherapy in combination with surgery, up to 20% of patients recur after primary treatment with poor prognosis. To gain insights into the mechanism of recurrence to inform patient stratification and precision treatment, we carried out RNA-seq analysis on 43 HPV+ HNSCC specimens, of which 15, including 7 recurrent tumors, were analyzed by quantitative mass spectrometry. The proteome and phosphoproteome, but not the transcriptome, were found to be distinct between the recurrent and non-recurrent tumors. Specifically, recurrent tumors featured a pro-fibrotic and immune suppressive tumor microenvironment (TME) characterized with more abundant cancer associated fibroblasts, extracellular matrix (ECM), neutrophils and suppressive myeloid cells, increased potential for epithelial-mesenchymal transition and defective T cell function, accompanied by aberrant changes in the corresponding signaling pathways. Mechanistically, kinome reprogramming played a pivotal role in mediating recurrence through regulating TME remodelling, cytoskeletal reorganization, cell adhesion, neutrophil function, and coagulation. Besides providing systems-level insights into the molecular basis of recurrence, our work led to the identification of numerous mechanism-based biomarkers and therapeutic targets that may aid future endeavours of developing prognostic biomarkers and precision medicine for recurrent HPV+ HNSCC.
2022-06-01 | PXD030343 | Pride
Project description:The conserved Hippo-YAP signaling pathway is involved in homeostasis and organ development through the regulation of cell growth and cell death. Its downstream effectors YAP1, WWTR1 (TAZ), and TEAD are transcriptionally active in the majority of human cancers, often as a result of copy-number variation or inactivating mutations of core components and upstream regulators. Analysis of The Cancer Genome Atlas and other published data of head and neck squamous cell carcinoma (HNSCC) reveals somatic alterations of the Hippo-YAP pathway in approximately 50% of HNSCC, making it the most altered pathway in these cancers. Unfortunately, highly specific inhibitors targeting the YAP1 transcriptional complex are not available, and better strategies to target this pathway are sought. Here, we show that FAT1 (FAT Atypical Cadherin 1), an upstream inhibitor of YAP1, is mutated either by missense or truncating mutation in 29% of HNSCC. Comprehensive proteomic and drug-screening studies across pan-cancer models confirm that FAT1-mutant HNSCC exhibit selective and higher sensitivity to BRD4 inhibition by JQ1. Epigenomic analysis reveals an active chromatin state in FAT1-mutant HNSCC cells that is driven by the YAP/TAZ transcriptional complex through recruitment of BRD4 to deposit active histone marks, thereby maintaining an oncogenic transcriptional state. This study reveals a detailed cooperative mechanism between YAP1 and BRD4 in HNSCC and suggests a specific therapeutic opportunity for the treatment of this subset of head and neck cancer patients.
2023-10-01 | GSE202036 | GEO
Project description:Overall survival remains very poor for patients diagnosed with head and neck squamous cell carcinoma (HNSCC). Identification of additional biomarkers and novel therapeutic strategies are important for improving patient outcome. Patient-derived xenografts (PDXs), generated by implanting fresh tumor tissue directly from patients into immune-deficient mice, recapitulate many of the features of their corresponding clinical cancers, including histopathological and molecular profiles. Using a large collection of PDX models of HNSCC we demonstrate that rapid engraftment into immune-compromised mice is highly prognostic, and show that genomic deregulation of the G1/S checkpoint pathway correlates with engraftment. Furthermore, CCND1 and CDKN2A genomic alterations are predictive of response to the CDK4/6 inhibitor abemaciclib. Overall, our study supports the pursuit of CDK4/6 inhibitors as a therapeutic strategy for a substantial proportion of HNSCC patients, and demonstrates the potential of using PDX models to identify novel targeted therapies for those patients who have the poorest outcomes.
| EGAS00001002979 | EGA
Project description:Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial–mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.
2015-06-02 | GSE61231 | GEO
Project description:Mucin 1 (MUC1) is aberrantly expressed in adenocarcinomas of epithelial barrier tissues and contributes to their progression. Less is known about involvement of MUC1 in the pathogenesis of squamous cell carcinomas (SCCs). The present work demonstrates that the MUC1 gene is upregulated in advanced head and neck SCCs (HNSCCs) and, as determined by scRNA-seq analysis, is expressed in the malignant cell populations of HNSCC tumors. Studies of HNSCC cell lines demonstrate that the MUC1-C subunit regulates expression of (i) RIG-I and MDA5 pattern recognition receptors, (ii) STAT1 and interferon (IFN) regulatory factors, and (iii) downstream IFN-stimulated genes (ISGs). MUC1-C integrates STAT1 with induction of the ∆Np63 and SOX2 genes that are aberrantly expressed in HNSCCs. We also show that MUC1-C/STAT1 signaling activates the NFE2L2 gene and, in turn, MUC1-C binds directly to NRF2 in regulating redox balance. In extending these HNSCC cell dependencies, we demonstrate that MUC1-C is necessary for NOTCH3 expression, self-renewal capacity and tumorigenicity. These results indicate that MUC1-C is a common effector that integrates STAT1-mediated chronic inflammation with regulation of the ∆Np63, SOX2, NRF2 and NOTCH3 TFs. Our findings indicate that MUC1-C drives progression of the HNSCC CSC state and is a target for advanced HNSCC treatment.
2024-04-23 | GSE252287 | GEO