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PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

ABSTRACT: PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

PROVIDER: PRJNA601436 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10898858_1.fastq.gz	Fastqsanger.gz
	SRR10898858_2.fastq.gz	Fastqsanger.gz
	SRR10898859_1.fastq.gz	Fastqsanger.gz
	SRR10898859_2.fastq.gz	Fastqsanger.gz
	SRR10898860_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

PIK3CA and p53 mutations promote 4NQO-initated head and neck tumor progression and metastasis in mice

Project description:The effect of gain of function mutations in p53, pik3ca, and both genes in mouse tongue subject to 4NQO treatment on gene expression is characterized by RNASeq.

2022-04-19 | GSE143716 | GEO

A head and neck cancer protein interaction map reveals PIK3CA mutant drug sensitivity

Project description:Despite extensive DNA sequencing of patient tumors, it remains challenging to translate the immense landscape of heterogeneous genetic alterations into function and clinical outcomes due to a limited understanding of cancer specific molecular network architectures. To bridge this gap, we have used affinity purification-mass spectrometry to generate protein interaction networks for 31 proteins with significant alterations in head and neck squamous cell carcinoma. This network includes 771 interactions covering both cancer and non-tumorigenic cell states, as well as wild-type and mutant proteins. Differential analysis across these dimensions reveals a strong interaction between PIK3CA and ERBB3 (HER3), dependent upon mutations in PIK3CA. We show that this interaction correlates with ERBB3 activity in vitro and can be targeted in vivo using a clinical ERBB3 inhibitor, CDX3379, to prohibit growth of tumors with common PIK3CA mutations. This study provides a roadmap for elucidating genetic complexity through multidimensional maps of cancer cell biology.

2021-10-07 | PXD019469 | Pride

Transcriptomic analysis of head and neck cancer stable cell lines [RNA-seq, p53 R273H, MCM5]

Project description:Gain-of-function mutant p53 can function through a mutp53-MCM5-Sting-noncanonical NFkB signaling axis. We will analyze the transcriptional profiles of head and neck cancer stable cell lines UM-SCC-1 with overexpression of R273H mutant p53 and/or MCM5 under the normal culture condition.

2023-11-29 | GSE165374 | GEO

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

Project description:Objectives: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved. Material and methods: Mutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n=243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n=62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n=91). Results: Only high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors. Conclusions: High expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

2018-04-02 | GSE95805 | GEO

<i>PIK3CA</i> and <i>p53</i> Mutations Promote 4NQO-Initated Head and Neck Tumor Progression and Metastasis in Mice.

Project description:The PI3K signaling pathway is frequently mutated in head and neck squamous cell carcinoma (HNSCC), often via gain-of-function (GOF) mutations in the PIK3CA gene. Here, we present novel genetically engineered mouse models (GEMM) carrying a GOF allele Loxp-STOP-Loxp(LSL)-PIK3CAH1047R (E20) alone or in combination with heterozygous LSL-p53+/R172H (p53) mutation with tissue-specific expression to interrogate the role of oncogenic PIK3CA in transformation of upper aerodigestive track epithelium. We demonstrated that the GOF PIK3CA mutation promoted progression of 4-nitroquinoline 1-oxide-induced oral squamous cell carcinoma (OSCC) in both E20 single mutant and E20/p53 double mutant mice, with frequent distal metastasis detected only in E20/p53 GEMM. Similar to in human OSCC, loss of p16 was associated with progression of OSCC in these mice. RNA-seq analyses revealed that among the common genes differentially expressed in primary OSCC cell lines derived from E20, p53, and E20/p53 GEMMs compared with those from the wild-type mice, genes associated with proliferation and cell cycle were predominantly represented, which is consistent with the progressive loss of p16 detected in these GEMMs. Importantly, all of these OSCC primary cell lines exhibited enhanced sensitivity to BYL719 and cisplatin combination treatment in comparison with cisplatin alone in vitro and in vivo, regardless of p53 and/or p16 status. Given the prevalence of mutations in p53 and the PI3K pathways in HNSCC in conjunction with loss of p16 genetically or epigenetically, this universal increased sensitivity to cisplatin and BYL719 combination therapy in cancer cells with PIK3CA mutation represents an opportunity to a subset of patients with HNSCC. IMPLICATIONS: Our results suggest that combination therapy of cisplatin and PI3K inhibitor may be worthy of consideration in patients with HNSCC with PIK3CA mutation.

| S-EPMC7272268 | biostudies-literature

Head and neck squamous cell carcinoma

Project description:Quantitative (iTRAQ 4-plex) proteomic analysis of progressive head and neck cancers

2022-03-01 | PXD001438 | Pride

Gene expression profiles of head and neck squamous cell carcinoma

Project description:Sage performed on microdissection of Head and Neck tumor, and Head and Neck normal tissue comparative analysis of gene expression profiles of head and neck squamous cell carcinoma and Head and Neck normal tissue

2008-09-30 | E-GEOD-11986 | biostudies-arrayexpress

The dual pathway inhibitor rigosertib is effective in direct-patient tumor xenografts of head and neck squamous cell carcinomas

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

Transcriptomic analysis of head and neck cancer stable cell lines [RNA-seq]

Project description:Gain-of-function mutant p53 can function through a mutp53-MCM5-Sting-noncanonical NFkB signaling axis. We will analyze the transcriptional profiles of head and neck cancer stable cell lines UM-SCC-1 and MDA1586 with overexpression or downregulation of mutant p53 in the presence or absence of Sting or RelB knockdown under the normal culture condition

2023-11-29 | GSE164432 | GEO

Transcriptomic analysis of head and neck cancer stable cell lines [RNA-seq_HU]

Project description:Gain-of-function mutant p53 can function through a mutp53-MCM5-Sting-noncanonical NFkB siganling axis. We will analyze the transcriptional profils of head and neck cancer stable cell lines UM-SCC-1 and MDA1586 with overexpression or downregulation of mutant p53 in the presence or absence of Sting or RelB knockdown under the treatment with or without hydroxyurea.

2023-11-29 | GSE163675 | GEO

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