YAP and/or TAZ inhibition in HepG2 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE137915 | GEO | 2020/05/12
REPOSITORIES: GEO
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Project description:The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer types. However, to which extent YAP and TAZ cooperatively contribute to cholangiocarcinoma (CCA) development and progression is poorly understood. Our immunohistochemical studies showed that YAP and TAZ were expressed in different CCA subtypes. However, nuclear co-expression was not frequently detected. RNAinterference (RNAi) experiments illustrated that YAP and TAZ supported CCA cell viability. Comprehensive expression profiling of HUCCT-1 cells after combined silencing of YAP/TAZ revealed a potential impact on chromosomal instability.
2021-10-01 | GSE172135 | GEO
Project description:YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Here we sought to evaluate which genes are regulated by endogenous levels of YAP/TAZ. We compared SK-N-MC cells transfected with a control non-targeting siRNA with cells transfected with a mix of siRNA targeting both YAP and TAZ.
2018-09-27 | GSE120512 | GEO
Project description:The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, also called WWTR1), the main effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in cancer. We aim to compare the transcriptome altered by knockdown of YAP, TAZ or both using siRNA in MDA-MB-231 (derived from human metastatic breast adenocarcinoma).
2023-03-20 | GSE205726 | GEO
Project description:YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.
2015-03-23 | GSE59229 | GEO
Project description:YAP1 (Yes-associated protein 1) and TAZ (transcriptional coactivator with PDZ-binding motif, or WWTR1) are nucleo-cytoplasmic shuttling proteins that can function in the nucleus as transcriptional coactivators. Their role in regulating gene transcription has been so far mainly investigated by overexpressing YAP1 or TAZ, while here we sought to determine which genes are regulated by endogenous levels of YAP/TAZ. To this end, we compared MCF10A cells transfected with a control non-targeting siRNA to cells transfected with two independent mixes of siRNA targeting both YAP and TAZ.
2015-03-23 | GSE59230 | GEO
Project description:The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors, with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. We sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. We showed that the two paralogs orchestrate non-overlapping transcription programs in this cancer type.
2020-07-24 | GSE151200 | GEO
Project description:The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors, with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. We sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. We showed that the two paralogs orchestrate non-overlapping transcription programs in this cancer type.
2020-07-24 | GSE151199 | GEO
Project description:Background & Aims: Succinate dehydrogenase enzyme (SDH) is frequently found to be diminished in Hepatocellular carcinoma (HCC) patient samples, and SDH reduction is associated with elevated succinate level and poor prognosis in HCC patients. But the underlying mechanisms about how impaired SDH activity promotes HCC malignancy remain unclear. Approach & Results: In this study, we observed remarkable downregulations of SDH subunits A and B (SDHA/B) in chronic liver injury-induced murine HCC models and HCC patient samples. Subsequent RNA sequencing, hematoxylin & eosin (H&E) staining and immunohistochemistry (IHC) analyses of HCC samples revealed that Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) were significantly upregulated in HCC, with their levels inversely correlating with that of SDHA/B. The protein stability of YAP/TAZ was greatly enhanced in SDHA/B-depleted HCC cells along with accumulation of succinate. Further mechanistic analyses demonstrated that impaired activity of SDHA/B resulted in succinate accumulation which facilitated the removal of NEDDylation on cullin1, therefore disrupted the E3 ubiquitin ligase SCFβ-TrCP complex, consequently led to YAP/TAZ stabilization and activation in HCC cells. The accelerated in vitro cell proliferation and in vivo tumor growth caused by SDHA/B reduction or succinate exposure were largely dependent on the aberrant activation of YAP/TAZ. Conclusions: Our study demonstrated that SDHA/B reduction promotes HCC proliferation by preventing the proteasomal degradation of YAP/TAZ through modulating cullin1 NEDDylation, thus addicts SDH-deficient HCC cells to YAP/TAZ pathway and renders these cells vulnerable to YAP/TAZ inhibition. Our findings warrant further investigation on the therapeutic effects of targeting YAP/TAZ in HCC patients displaying reduced SDHA/B or elevated succinate levels.
2023-05-31 | GSE207147 | GEO
Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.
2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress
Project description:Abstract Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. Taz was expressed in activated satellite cells. siRNA knockdown or constitutive expression of wildtype or constitutively active TAZ mutants showed that TAZ promoted proliferation, a function that was shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene symbol Wwtr1-/-) knockout mice, there were no overt effect on regeneration. However, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapflox/flox : Rosa26Lacz mice produced a marked regeneration deficit. To identify potential mechanisms, microarray analysis showed many common Taz/Yap targets, but Taz also regulates some genes independently of Yap, including myogenic genes such as Pax7, Myf5 and Myod1. Proteomic analysis of Yap/Taz revealed many common binding partners, but Taz also interacts with proteins distinct from Yap, that are mainly involved in myogenesis and aspects of cytoskeleton organization. Neither TAZ nor YAP bind members of the Wnt destruction complex but both extensively changed expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to promote myogenic differentiation.
2017-06-13 | PXD005751 | Pride