Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 22 for “"TEAD"”.
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Exploring the Potential use of TEAD Inhibition as Part of a Combination Therapy for NF2-Deficient Schwannoma and Meningioma.
… Previous studies evaluating small molecule TEAD auto-palmitoylation inhibitors have distinguished their anti-proliferative effect in NF2-deficient cancers. Here we aim to identify compounds that could be utilised in conjunction with TEAD inhibition, to target aberrant Hippo signalling and …
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Taz As A Regulator of Mesenchymal Transformation and Clinical Aggressiveness In Gliomas
… the expression of TAZ, its binding partner TEAD, and the mesenchymal marker FN1 in human gliomas. Western analyses demonstrated increased expression of TAZ, TEAD4, and FN1 in GBM relative to lower grade gliomas. We also identified CpG islands in the TAZ promoter that are methylated in most …
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Analysis of Hippo pathway signalling in schwannoma and meningioma
… effectors of the Hippo signalling pathway, and TEAD, a group of transcription factors binding to YAP and TAZ. There resulting gene expression is associated with increased proliferation and evasion of cell death. This makes the YAP/TAZ-TEAD complex an excellent therapeutic target. Since therapy …
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The Role of Hippo Signalling in Merlin Null Tumours of the Nervous System
… transcription, primarily by binding to the TEAD family of transcription factors, which has been linked to multiple tumour phenotypes. Here we aim to show that aberrant Hippo pathway activity in Merlin null meningioma and schwannoma can be targeted either genetically or pharmacologically to …
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The Role of YAP/TAZ in von Willebrand Factor Gene Expression
… function predominantly through interactions with TEAD transcription factors to regulate transcription of target genes, which ultimately execute the physiological output of upstream signalling mechanisms. Mechanical signals, such as shear stress, contribute to regulating YAP/TAZ with high shear …
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A Structure-Activity Relationship Study with Isoquinolinone Compounds and Stromal Antigen 2 Mutant Ewing’s Sarcoma Cells and Synthesis of Small Molecules for Anticancer Activity Through TEAD Palmitoylation Inhibition
… and prevent cancer cell proliferation, the TEAD protein is prohibited from undergoing palmitoylation, in which cell proliferation and anti-apoptosis is prevented. Two small hydrophobic structures were discovered through virtual ligand screening by our collaborators. Two initial synthetic …
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Papel de YAP/TAZ en la respuesta de células tumorales a estímulos activadores de receptores de TRAIL
… al núcleo. Allí, se asocian con los factores TEAD, y regulan la expresión de genes que promueven supervivencia y proliferación celular. El aumento de la rigidez de la matriz extracelular correlaciona con una mayor supervivencia tumoral. En esta tesis doctoral, planteamos la hipótesis de que …
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Age-associated alterations in head and neck cancer
… and TEA-domain transcription factor family (TEAD) activity in oral carcinoma cells in old mice. We demonstrated that targeting YAP-TEAD activity restored the immunogenicity of oral carcinoma cells, enhancing immune infiltration and tumor clearance in old mice. In additional studies, we …
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Interrogating therapeutic resistance to oncogenic KRASG12C-based therapies in colorectal cancer
… combination. Moreover, we identify YAP-TAZ TEAD as a mechanism of acquired resistance in both our in vivo resistant models and in progressing patients. Finally, we interrogate novel YAP and pan-TEAD inhibitors for their clinical potential to overcome emergent resistance to KRASG12C and EGFR …
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Development of drug screening assays for identification of new molecules against pancreatic ductal adenocarcinoma
… mechanism of action of the identified compound. TEAD is the major transcriptional factor partner in the functional activity of YAP and CTGF is considered one of the main representative target genes whose expression is regulated by this couple of transcriptional regulators.Chromatin …
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Endogenous retroviral proteins as potential drug targets for merlin-deficient tumours
… that HERV-K Env overexpression is regulated by TEAD-mediated transcription both in Merlin-deficient schwannoma and grade I meningioma. Furthermore, I have successfully tested the FDA approved retroviral protease inhibitors Ritonavir, Atazanavir and Lopinavir which could be potentially repurposed …
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Molecular mediators of cardiac-specific enhancer activation
… these data, we identified the TEA domain family (TEAD) TF TEAD1 as a candidate regulator of enhancer activation during cardiac-lineage commitment. We then used an inducible degron-tag strategy to conditionally deplete TEAD1 and observed an abnormal beating phenotype in CMs. Further mechanistic …
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Identifying the Molecular Mechanism of TAZ-Induced Lung Tumorigenesis
… TAZ and its major binding transcription factor TEAD. Together, our study shows for the first time a new mechanism linking PI3K and TGF-ß pathways to TAZ-induced cell transformation, suggesting TAZ as a therapeutic target for NSCLC.
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Vestigial-Like 1 Is A Shared Targetable Cancer-Placenta Antigen Expressed By Pancreatic and Basal-Like Breast Cancers
… VGLL1 shares a similar binding motif to the TEAD family of genes with the oncogenes, YAP/TAZ that promote malignancies through the Hippo signaling pathway. We show that VGLL1 may play a significant role in tumorigenesis by inducing tumor cell proliferation, migration, and invasion.</p>
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Identification of Oncogenic KRAS-Associated Vulnerabilities in Non-Small Cell Lung Cancer
… was reversed by coadministration of YAP1/TEAD inhibitor. Thus, our study suggests that XPO1 can be exploited for a promising therapeutic opportunity for KRAS mutant lung cancer and provides strategies for genomics-guided application of clinically available XPO1 inhibitors.
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YAP and TAZ have Functionally Redundant Roles in Uveal Melanoma
… that the tumorigenic effects of YAP and TAZ are TEAD-dependent. To determine the human relevance, multiple YAP or TAZ-deficient clones were generated for two human UM cell lines, Mel202 and MP41. Deletion of either protein had no consistent deleterious effects on cell survival or proliferation, …
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Genome-wide identification of enhancers, transcription factors, and mechanisms that control skeletal muscle differentiation in cattle
… with binding sites for MyoD, AP-1, AP-4, KLF, TEAD, and MEF2 transcription factors. Through siRNA-mediated knockdown, AP-4 was found to be essential for differentiation of bovine satellite cells into myotubes. The objective of the third study was to identify enhancers and transcription factors …
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Biophysical profiling of YAP/TAZ dependent mechanical responses
… activation. This activation elevates specific TEAD-mediated downstream gene targets involved in the dynamic regulation of cell volume. Meanwhile, cellular responses to stiffness using both elastic supported surface dishes and hydrogel were explored. HEK293A responses to variations in stiffness …
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The Hippo Signaling Pathway in Organ Size Control and Regeneraton
… transcriptional coactivator Yorkie (Yki) and the TEAD/TEF family of transcription factor Scalloped (Sd) in Drosophila. The inhibition of Yki activity is through modulating its phosphorylation status and subcellular localization by upstream kinase complex. I obtained both genetic and cellular …
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Regulation of Cardiomyocyte Proliferation by microRNAs and Small Molecules
… of YAP and stimulate transcription of TEAD-responsive genes. The second part of the project was aimed at identifying small molecules exerting a mitogenic effect on neonatal cardiomyocytes through an unbiased high-throughput screening (HTS) of a library of 780 FDA-registered drugs. The …
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