Cells to Investigate How ACTL6A and p63 Activate Hippo-YAP in SCC
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ABSTRACT:
PROVIDER: PRJNA348817 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4428793.fastq.gz | Fastqsanger.gz | |||
| SRR4428794.fastq.gz | Fastqsanger.gz |
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Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC.
2016-11-18 | GSE88859 | GEO
Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of HNSCC cells with and without ablated endogenous ACTL6A via lentiviral shRNA.
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Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of HNSCC cells with and without ablated endogenous p63 via lentiviral shRNA
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Project description:Loss-of-function mutations in SWI/SNF chromatin remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here we reveal that ACTL6A, encoding a SWI/SNF subunit linked to stem and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact and cooperatively control a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1. Consequently, loss of ACTL6A or p63 in tumor cells induces YAP phosphorylation and inactivation, associated with growth arrest and terminal differentiation, all phenocopied by WWC1 overexpression. In vivo, ectopic ACTLC6A/p63 expression promotes tumorigenesis, while ACTL6A expression and YAP activation are highly correlated in primary HNSCC and predict poor patient survival. Thus, ACTL6A and p63 collaborate as oncogenic drivers in HNSCC. Gene expression profiling of untransformed keratinocytes (HaCaT) with and without ablated endogenous p63 via lentiviral shRNA.
2016-11-18 | GSE88832 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-11-18 | GSE88861 | GEO
Project description:This study was designed to examine the requirement for the p63 transcription factor in Squamous Cell Carcinoma (SCC) tumor maintenance in an in vivo murine system. A tamoxifen-inducible Keratin 14-driven Cre recombinase transgene was used to conditionally excise p63 in advanced murine SCC tumors. These data show the context-dependent regulation of p63 target genes in cancer.
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Project description:Aberrant expression of transcriptional regulators can affect oncogenic gene expression programs in cancer. Mutations in the tumor suppressor p53 are commonly found in UV-damaged skin and protect damaged epidermal cells from senescence and or oncogene-induced apoptosis, favoring cancer formation. In contrast, the other p53 family members p63 and p73 are rarely mutated in cancer and p63 is often amplified or overexpressed in lung, esophagus, and head and neck squamous cell carcinoma (SCC). Here, we demonstrate that both p63 and p73 are required for cell proliferation in epidermal cells and in skin SCC and are overexpressed in preneoplastic lesions and in skin SCCs. p63/p73 form heterotetramers and co-occupy thousands of regulatory regions, jointly controlling a transcriptional program that promotes cell proliferation and tumorigenesis. The combination of gene knockdown with transcriptomic and epigenetic analyses revealed that p63 and p73 control a transcriptional feed-forward circuit that sustains cell proliferation. We find that in skin SCC a key signaling pathway downstream of p63/p73 is the Epidermal Growth Factor Receptor (EGFR)/MAP kinase. p63/p73 directly and positively control transcription of the EGFR ligands, among which amphiregulin (AREG) is the most highly expressed in skin SCC. Like p63/p73, AREG is critical to maintain skin SCC proliferative potential, anchorage independent growth, and to promote tumorigenesis. Thus, p63 and p73 act as oncogenic drivers in skin SCC, with AREG being a crucial non-cell-autonomous effector downstream of p63 and p73 in skin SCC formation.
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Project description:This study was designed to examine the requirement for the p63 transcription factor in Squamous Cell Carcinoma (SCC) tumor maintenance in an in vivo murine system. A tamoxifen-inducible Keratin 14-driven Cre recombinase transgene was used to conditionally excise p63 in advanced murine SCC tumors. These data show the context-dependent regulation of p63 target genes in cancer. Total RNA from murine Squamous Cell Carcinoma tumors was examined 1-3 days following genomic excision of TP63 in Keratin 14-expressing tumor cells.
2013-08-06 | E-GEOD-45929 | biostudies-arrayexpress
Project description:ChIP-Seq Samples for p63 in HNSCC Cells to Investigate How ACTL6A and p63 Activate Hippo-YAP in SCC
| PRJNA348821 | ENA