VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300 DOI Open Access
Susu Guo, Xiaodi Hu, Jennifer L. Cotton

et al.

Published: July 1, 2024

Studies on Hippo pathway regulation of tumorigenesis largely center YAP and TAZ, the transcriptional co-regulators TEAD. Here, we present an oncogenic mechanism involving VGLL TEAD fusions that is pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. demonstrate that, contrast to VGLL2 TEAD1, fusion proteins are strong activators TEAD-dependent transcription, their function does not require YAP/TAZ. Furthermore, identify TEAD1 engage specific epigenetic by recruiting histone acetyltransferase p300 control TEAD-mediated landscapes. showed small molecule inhibition can suppress proteins-induced transformation both vitro vivo . Overall, our study reveals a molecular basis for involvement cancer provides framework targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Language: Английский

Basic mechanism of mobilizing cell movement during invasion of glioblastoma and target selection of targeted therapy DOI Creative Commons
Jie Xu, Pengfei Shi, Liqun Yang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Glioblastoma (GBM), also known as glioblastoma multiforme, is a rapidly growing and highly invasive malignant tumor. Due to the inability clearly distinguish between normal tissue, surgery cannot achieve safe resection, often leading poor patient prognosis inevitable tumor recurrence. According previous studies, GBM invasion related intercellular adhesion, matrix degradation, extracellular its adhesion molecules, well molecular of protein hydrolases in microenvironment cells stromal cells. The aim enhance our understanding mechanisms underlying advance research on targeted therapies for inhibiting invasion. This article describes that may affect cell invasion, changes cytoskeleton during motility, regulatory intracellular signaling pathways In addition, we explored possibility therapy against molecules GBM.

Language: Английский

Citations

0
YAP/TAZ: An Epitome of Tumorigenesis DOI
Soumya Mukherjee,

Emily A Warden,

Jianmin Zhang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217806 - 217806

Published: May 1, 2025

Language: Английский

Citations

0
Nuclear ubiquitination permits Hippo–YAP signal for liver development and tumorigenesis DOI
Jinsong Wei, Zhifa Cao, Qing Li

et al.

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 16, 2025

Language: Английский

Citations

0
Inhibition of the YAP-MMB interaction and targeting NEK2 as potential therapeutic strategies for YAP-driven cancers DOI Creative Commons
Marco Jessen,

Dörthe Gertzmann,

Franziska Liss

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(8), P. 578 - 593

Published: Jan. 5, 2024

Abstract YAP activation in cancer is linked to poor outcomes, making it an attractive therapeutic target. Previous research focused on blocking the interaction of with TEAD transcription factors. Here, we took a different approach by disrupting YAP’s binding factor B-MYB using MY-COMP, fragment containing domain fused nuclear localization signal. MY-COMP induced cell cycle defects, abnormalities, and polyploidization. In AKT YAP-driven liver model, significantly reduced tumorigenesis, highlighting importance YAP-B-MYB tumor development. also perturbed progression YAP-dependent uveal melanoma cells but not YAP-independent cutaneous lines. It counteracted expression MMB-regulated genes, explaining observed effects. We identified NIMA-related kinase (NEK2) as downstream target B-MYB, promoting transformation facilitating centrosome clustering inhibiting multipolar mitosis.

Language: Английский

Citations

3
YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets DOI
Bingyu Ye,

Meijuan Yue,

Chen Hu

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Dec. 24, 2024

Language: Английский

Citations

2
The Hippo pathway: organ size control and beyond DOI
Pengfei Guo,

Sicheng Wan,

Kun‐Liang Guan

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 77(2), P. 100031 - 100031

Published: Dec. 25, 2024

The Hippo signaling pathway is a highly conserved network for controlling organ size, tissue homeostasis, and regeneration. It integrates wide range of intracellular extracellular signals, such as cellular energy status, cell density, hormonal mechanical cues, to modulate the activity YAP/TAZ transcriptional coactivators. A key aspect regulation involves its spatial organization at plasma membrane, where upstream regulators localize specific membrane subdomains regulate assembly activation components. This critical precise control signaling, it dictates dynamic interactions between components their regulators. Recent studies have also uncovered role biomolecular condensation in regulating adding complexity mechanisms. Dysregulation implicated various pathological conditions, particularly cancer, alterations contribute tumorigenesis drug resistance. Therapeutic strategies targeting shown promise both cancer treatment, by inhibiting regenerative medicine, enhancing promote repair. development small molecule inhibitors YAP-TEAD interaction other offers new avenues therapeutic intervention. SIGNIFICANCE STATEMENT: regulator regeneration, with dysregulation linked diseases cancer. Understanding this opens possibilities approaches medicine oncology, potential translate basic research into improved clinical outcomes.

Language: Английский

Citations

2
Hypoxia‐sensing VGLL4 promotes LDHA‐driven lactate production to ameliorate neuronal dysfunction in a cellular model relevant to Alzheimer's disease DOI
Qiuyun Tian, Junjie Li, Bin Wu

et al.

The FASEB Journal, Journal Year: 2023, Volume and Issue: 37(12)

Published: Nov. 3, 2023

Alzheimer's disease (AD) is a neurodegenerative where abnormal amyloidogenic processing of amyloid-β precursor protein (APP) occurs and has been linked to neuronal dysfunction. Hypometabolism glucose in the brain can lead synaptic loss death, which turn exacerbates energy deficiency peptide (Aβ) accumulation. Lactate produced by anaerobic glycolysis serves as an substrate supporting function facilitating repair. Vestigial-like family member 4 (VGLL4) recognized key regulator hypoxia-sensing pathway. However, role VGLL4 AD remains unexplored. Here, we reported that expression was significantly decreased tissue model mice cells. We further found overexpression reduced APP ameliorated damage. Notably, identified compromised hypoxia-sensitive capability LDHA regulated context AD. Upregulation increased response hypoxia enhanced levels lactate inhibiting ubiquitination degradation LDHA. Furthermore, inhibition production using sodium oxamate, inhibitor LDHA, suppressed neuroprotective increasing processing. Taken together, our findings demonstrate exerts effect upregulating consequently promoting production. Thus, this study suggests may be novel player involved molecular mechanisms relevant for ameliorating neurodegeneration.

Language: Английский

Citations

5
VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300 DOI Creative Commons
Susu Guo, Xiaodi Hu, Jennifer L. Cotton

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

Abstract Studies on Hippo pathway regulation of tumorigenesis largely center YAP and TAZ, the transcriptional co-regulators TEAD. Here, we present an oncogenic mechanism involving VGLL TEAD fusions that is pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. demonstrate that, contrast to VGLL2 TEAD1, fusion proteins are strong activators TEAD-dependent transcription, their function does not require YAP/TAZ. Furthermore, identify TEAD1 engage specific epigenetic by recruiting histone acetyltransferase p300 control TEAD-mediated landscapes. showed small molecule inhibition can suppress proteins-induced transformation both vitro vivo . Overall, our study reveals a molecular basis for involvement cancer provides framework targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Language: Английский

Citations

1
VGLL2 and TEAD1 fusion proteins drive YAP/TAZ-independent transcription and tumorigenesis by engaging p300 DOI Open Access
Susu Guo, Xiaodi Hu, Jennifer L. Cotton

et al.

Published: July 1, 2024

Studies on Hippo pathway regulation of tumorigenesis largely center YAP and TAZ, the transcriptional co-regulators TEAD. Here, we present an oncogenic mechanism involving VGLL TEAD fusions that is pathway-related but YAP/TAZ-independent. We characterize two recurrent fusions, VGLL2-NCOA2 TEAD1-NCOA2, recently identified in spindle cell rhabdomyosarcoma. demonstrate contrast to VGLL2 TEAD1, fusion proteins are strong activators TEAD-dependent transcription, their function does not require YAP/TAZ. Furthermore, identify TEAD1 engage specific epigenetic by recruiting histone acetyltransferase p300 control TEAD-mediated landscapes. showed small molecule inhibition can suppress proteins-induced transformation both vitro vivo . Overall, our study reveals a molecular basis for involvement cancer provides framework targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Language: Английский

Citations

1
Maternal vgll4a regulates zebrafish epiboly through Yap1 activity DOI Creative Commons

Carlos Camacho-Macorra,

Noemí Tabanera,

Elena Sánchez-Bustamante

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 20, 2024

Gastrulation in zebrafish embryos commences with the morphogenetic rearrangement of blastodermal cells, which undergo a coordinated spreading from animal pole to wrap around egg at vegetal pole. This rearrangement, known as epiboly, relies on orchestrated activity maternal transcripts present egg, compensating for gradual activation zygotic genome. Epiboly involves mechano-transducer yap1 but what are regulators and whether these maternally or zygotically derived remain elusive. Our study reveals crucial role vgll4a, proposed Yap1 competitor, during epiboly. In lacking maternal/zygotic vgll4a (MZ ), progression epiboly blastopore closure is delayed. delay associated ruffled appearance sliding epithelial decreased expression yap1-downstream targets transient impairment actomyosin ring syncytial layer. also shows that, rather than competing yap1, modulates levels E-cadherin/β-catenin adhesion complex blastomeres’ plasma membrane hence their actin cortex distribution. Taking results together, we propose that acts initiation upstream complex, contributing proper balance between tissue tension/cohesion contractility, thereby promoting timely progression.

Language: Английский

Citations

1