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PROVIDER: PRJNA172010 | ENA |
REPOSITORIES: ENA
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Project description:Role of TAZ as mediator of Wnt signaling (SW480)
| PRJNA172012 | ENA
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
Project description:The transcriptional co-activator TAZ/WWTR1 plays a central role in the Hippo signaling pathway and acts as crucial mediator in maintaining organ size and tissue homeostasis. Changes in its activity can lead to diseases, including cancer, due to uncontrolled cell growth or aberrant cellular behavior. The aim of this study was to identify gene signatures that are specifically regulated by TAZ in human trophoblast cells. This was achieved by comparing JEG-3 wild-type and TAZ knockout choriocarcinoma cells, generated with CRISPR-Cas9 technology.
2025-03-28 | GSE282831 | GEO
Project description:In melanoma, a switch from a proliferative melanocytic to an invasive mesenchymal phenotype is based on dramatic transcriptional reprogramming which involves complex interactions between a variety of signaling pathways and their downstream transcriptional regulators. TGFb/SMAD, Hippo/YAP/TAZ and Wnt/b-catenin signaling pathways are major inducers of transcriptional reprogramming and converge at several levels. Here, we report that TGFb/SMAD, YAP/TAZ and b-catenin are all required for a proliferative-to-invasive phenotype switch. Loss and gain of function experimentation, global gene expression analysis, and computational nested effects models revealed the hierarchy between these signaling pathways and identified shared target genes. SMAD-mediated transcription at the top of the hierarchy leads to the activation of YAP/TAZ and of b-catenin, with YAP/TAZ governing an essential sub-program of TGFb-induced phenotype switching. Wnt/b-catenin signaling is situated further downstream and exerts a dual role: it promotes the proliferative, differentiated melanoma cell phenotype and it is essential but not sufficient for SMAD or YAP/TAZ-induced phenotype switching. The results identify epistatic interactions among the signaling pathways underlying melanoma phenotype switching and highlight the priorities in targets for melanoma therapy.
2021-11-11 | GSE188463 | GEO
Project description:Tissue-specific regulation of WNT and YAP/TAZ signaling is critical for optimal organismal growth, development, and maintenance. Uncontrolled activity often leads to developmental abnormalities and aggressive cancers. Tankyrase (TNKS) is a poly-ADP-ribose polymerase (PARP) that controls both WNT and YAP/TAZ signaling. However, it is unclear how TNKS activity is regulated in a tissue and cell-type specific manner. Here, we identified the previously uncharacterized prostate-associated gene 4 (PAGE4) as a tissue-specific TNKS inhibitor. Structural and biochemical studies revealed that mechanistically PAGE4 inhibits TNKS through hijacking TNKS substrate binding pockets leading to the stabilization of TNKS substrates. In vitro cell culture and in vivo zebrafish and transgenic mouse model studies showed that PAGE4 is a potent inhibitor of TNKS and WNT signaling. Interestingly, PAGE4 is physiologically restricted to expression in select tissues and cell types, including WNT producing prostatic fibroblasts where spatiotemporal regulation of WNT signaling is critical for proper organ development. Surprisingly, PAGE4 is aberrantly expressed in hepatocellular carcinomas that bypass TNKS through mutant CTNNB1 driven WNT signaling. In vitro and in vivo tumorigenic studies revealed that PAGE4 initially function as a tumor suppressor through inhibition of WNT signaling, but upon CTNNB1 mutation becomes an oncogenic driver through YAP/TAZ signaling. Thus, we establish PAGE4 as a robust tissue-specific TNKS inhibitor that physiologically coordinates developmental WNT signaling, but genetic aberration during cancer progression re-wire PAGE4 into pro-oncogenic YAP/TAZ pathway.
2020-12-01 | GSE141323 | GEO
Project description:To investigate the role of TAZ downstream of the abberrant Wnt signaling in CRC cells, we compared the expression profiles of parental SW480 cells (empty vector) transfected with siControl, siTAZ, sibeta-catenin or reconstituted with wild type APC and transfected with siControl Keywords: expression profiling by array
2012-12-21 | GSE39904 | GEO
Project description:Promoting rumen development is closely related to the health and efficient growth of ruminants. In the present study, we aimed to assess the impact of YAP1/TAZ on RE proliferation. The transcriptomic expression was analyzed to investigate the potential regulatory networks. The results indicated that GA promoted RE cell proliferation, while VP disrupted RE cell proliferation. The Hippo, Wnt, and calcium signaling pathways were altered in cells following the regulation of YAP1/TAZ. Upon YAP1/TAZ activation through GA, the CCN1/2 increased to promote RE cell proliferation. While when the YAP1/TAZ was inhibited by VP, the BIRC3 decreased to suppress RE cell proliferation. Thus, YAP1/TAZ may be potential targets for regulating RE cell proliferation. These findings broaden our understanding of the role of YAP1/TAZ and their regulators in RE and offer a potential target for promoting rumen development.
2024-04-03 | GSE252747 | GEO
Project description:We show that Ror2 mediated non-canonical Wnt signaling in the dental mesenchyme plays a critical role in cell proliferation and thereby regulates root development size in mouse molars. Furthermore, Cdc42 acts as a potential downstream mediator of Ror2 signaling in root formation.
2020-11-13 | GSE161395 | GEO
Project description:The Hippo signaling pathway, mediated by its transcriptional effectors YAP and TAZ, play vital roles in maintaining lung homeostasis and facilitating injury repair. While the roles of the Hippo pathway in epithelial cells are well-established, its regulatory effects on lung fibroblasts remain less understood. Here, we engineered a novel mouse allele to allow inducible knockdown of YAP and TAZ, and show that fibroblast-specific knockdown enhances the ability of PDGFRa+ alveolar fibroblasts to support organoids derived from alveolar epithelial stem cells in vitro. Single-cell multiomic profiling revealed changes in fibroblast subpopulations, including the emergence of an Mmp9+ cluster containing Wnt4+ cells. Analyses demonstrated shifts in the epigenomic landscape leading to varied enrichment of transcription factor motifs across both fibroblasts and epithelial cells in response to targeted suppression of YAP/TAZ in fibroblasts. Further computational analyses identified an increase in epithelial Wnt signaling which was confirmed by in vivo studies. We found that Wnt4 expression was increased in PDGFRa-lineage+ fibroblasts and enhanced proliferation of SPC+ AT2 cells following fibroblast-specific YAP/TAZ knockdown. These results shed new light on the mechanistic role of YAP/TAZ in PDGFRa+ alveolar fibroblasts in supporting AT2 cell maintenance and proliferation via Wnt4 secretion.
2025-04-10 | GSE291640 | GEO