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YAP conveys an invasive phenotype to clear cell renal cell carcinoma cell lines via endothelin-2

ABSTRACT: To determine the biological mechanisms underlying the oncogenic properties of YAP in ccRCC the human ccRCC cell line MZ1774 was transduced with lentivirus containing a shRNA-cassette targeting YAP-mRNA. Expression profiles of MZ1774 YAP knockdown cells were compared to mock-transduced control cells. Total RNA from MZ1774 cells stably expressing shRNA directed against YAP compared to mock-transduced MZ1174 cells

ORGANISM(S): Homo sapiens

SUBMITTER: Moritz Kebschull

PROVIDER: E-GEOD-50053 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Hippo signaling mediates proliferation, invasiveness, and metastatic potential of clear cell renal cell carcinoma.

Schütte Ute U Bisht Savita S Heukamp Lukas C LC Kebschull Moritz M Florin Alexandra A Haarmann Jens J Hoffmann Per P Bendas Gerd G Buettner Reinhard R Brossart Peter P Feldmann Georg G

Translational oncology 20140304 2

Recent work has identified dysfunctional Hippo signaling to be involved in maintenance and progression of various human cancers, although data on clear cell renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and metastatic potential. Nuclear overexpression of the Hippo target Yes-associated protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was particularly prominent at the t ...[more]

PMID: 24913676

Similar Datasets

YAP conveys an invasive phenotype to clear cell renal cell carcinoma cell lines via endothelin-2

Project description:To determine the biological mechanisms underlying the oncogenic properties of YAP in ccRCC the human ccRCC cell line MZ1774 was transduced with lentivirus containing a shRNA-cassette targeting YAP-mRNA. Expression profiles of MZ1774 YAP knockdown cells were compared to mock-transduced control cells.

2014-12-23 | GSE50053 | GEO

Expression data of Cohesin-deficient, human cord blood-derived, hematopoietic CD34 cells

Project description:Decreased levels of Cohesin proteins increases the amount of primitive hematopoietic stem and progenitor cells in an in vitro setting. We used microarrays to detail the changes in global transcription programme to understand the underlying mechanisms behind this phenotype. Of note, we discover that hematopoietic stem cell-specific genes are upregulated in cells with decreased Cohesin levels. CD34 positive cells were isolated from human cord blood (not older than 24h), lentivirally transduced with shRNA targeting different members of the Cohesin complex. In order to focus on immediate changes, transduced cells were sorted 36 hours post transduction and analyzed.

2016-03-17 | E-GEOD-74824 | biostudies-arrayexpress

Effect of YAP overexpression on HuCCT1 cholangiocarcinoma cell line transcriptome (shRNA targeting YAP)

Project description:The YAP pathway in regulating organ size by integrating external signals to control the expression of genes involved in cell proliferation. YAP is known to be involved in tumorigenesis in several tissues, yet its role in cholangiocarcinoma is not established We used microarrays to assess the role of YAP pathway in cholangiocarcinoma either by overexpressing a constitutively active YAP1 mutant, or by downregulating YAP1 expression using shRNA HuCCT1 cells where transfected with either a control scrambled shRNA or a shRNA targeting YAP1; cells were harvested, RNA was collected and analyzed using microarray

2015-10-27 | E-GEOD-61765 | biostudies-arrayexpress

Quantitative analysis of YAP effects in podocytes

Project description:Human podocytes were transduced with mouse YAP, with mouse YAP 112A and with empty vector using lentiviral gene transfer. Effects of YAP were measured by quantitative proteomics.

2017-05-02 | PXD005182 | Pride

YAP targets TEAD4-NF-κB complex and inhibits ccRCC tumor growth

Project description:The prevalent understanding of Hippo signaling is one inhibitory pathway in tumor growth via deactivating the potential of YAP-TEAD transcriptional complex. The aberrant activation of YAP was observed in a series of human malignancies. However, recent studies implicate that in certain cancer types, YAP could be a tumor suppressor. Here, we reported a context-dependent function of YAP in clear cell renal carcinoma (ccRCC). Inhibition of Hippo kinase activity impeded ccRCC tumor growth and NF-κB transcriptional programs. Pharmacological blocking Hippo kinase activity or ectopic activation of YAP suppressed tumor growth in xenograft and PDX models. Mechanism studies revealed that TEAD could synchronize with P65 for NF-κB signaling activation, while YAP disrupted TEAD-NF-κB interactions and dissociated P65 from its target gene promoter, thereby inhibiting NF-κB transcriptional programs and ccRCC tumor growth. Our study identified a novel crosstalk between Hippo and NF-κB pathway, uncovered a non-canonical regulation of Hippo/YAP axis in renal cancer and suggested a novel strategy to ccRCC treatments by YAP activation.

2024-05-31 | GSE252142 | GEO

YAP targets TEAD-NF-κB complex and inhibits ccRCC tumor growth

2023-12-31 | GSE235788 | GEO

Transcription profiling by array of human MCF10A cells expressing YAP to identify the targets of the YAP oncogene

Project description:YAP is an oncogene and an inducer of Epithelial-to-Mesenchymal Transition (EMT). We used microarrays to detail the global program of gene expression to identify YAP target genes. PUBLICATION ABSTRACT:; The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Since this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS1 reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition (EMT), suggesting that this is a key feature of YAP signaling in mammalian cells. Experiment Overall Design: MCF10A cells were infected with retrovirus constructs (vector or YAP) and puromycin was used to select for transduced cells. Cells were split and grown to ~60-75%% confluency at which point they were harvested for RNA. Vector vs. YAP comparison was done in duplicate.

2008-06-11 | E-GEOD-10196 | biostudies-arrayexpress

Activation of Wnt signaling pathways in murine B16-F1 melanoma cells

Project description:Genome-wide transcriptional profiling using microarrays was used to compare gene regulation in B16 murine melanoma cells that were: 1) stably transduced with Wnt1-iresGFP; 2) stably transduced with Wnt3A-iresGFP; 3) stably transduced with Wnt5A-iresGFP; and 4) stably transduced with GFP and treated for 72 hours with 10 mM lithium chloride, a pharmacologic activator of canonical Wnt/beta-catenin signaling. Cells were sorted by fluorescence-activated cell sorting (FACS) to obtain populations with relatively equivalent levels of GFP expression. Biologic triplicates were used for each condition, and compared in two-channel hybridization to control RNA obtained from B16 cells expressing GFP (pooled from three biologic replicates).

2014-10-11 | E-MTAB-3012 | biostudies-arrayexpress

Expression data for HIF1alpha-regulated genes in clear cell renal carcinoma cells (ccRCC)

Project description:Gene expression profiling was performed in ccRCC cells, which either express both HIF1alpha and HIF2alpha (either naturally or by virtue of induced expression of HIF1alpha) or express HIF2alpha alone (either naturally or by virtue of a HIF1alpha shRNA), to identify genes regulated by HIF1alpha in ccRCC cells. Three H2 cell lines 769P, A498, and SLR24 were stably infected with retrovirus encoding doxycycline-inducible Luciferase (control) or HIF1alpha, and two H1H2 cell lines Caki-2 and SLR25 were stably infected with retroviruses encoding scrambled (control) or HIF1alpha shRNA. Duplicated samples were used for each condition.

2011-12-02 | E-GEOD-27415 | biostudies-arrayexpress

Nuclear YAP overexpression drives the human alveolar type 1 cell (AT1) cprogram in a cell autonomous manner in lentiviral transduced iPSC-derived alveolar type 2 cells (iAT2s)

Project description:SPC2B2 iAT2s were transduced with either control WT YAP or constitutively active nuclear YAP (YAP5SA) lentivirus in a single cell suspension and were then grown in iAT2 media (CK + DCI) in 3D matrigel for 7 days.

2023-08-08 | GSE221344 | GEO

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