Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD003120
PROVIDER: PRJNA300555 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-κB subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
2018-10-25 | PXD003120 | Pride
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53âs conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates
2015-12-11 | E-GEOD-74493 | biostudies-arrayexpress
Project description:We identified CTCF as a substrate of the LATS kinases. Under cellular stress conditions that activated LATS, CTCF was phosphorylated in a LATS-dependent manner and lost DNA-binding activity. LATS signaling target genes resided in CTCF-mediated insulated neighborhoods and depended on such chromatin organization to sustain their expression. Genome-wide CTCF DNA-binding profiling revealed that metabolic stress reduced CTCF occupancy specifically at a small subset of CTCF-binding sites that encompassed many LATS target genes and were most significantly associated with LATS signaling. Dissociation of CTCF from LATS target genes disrupted corresponding CTCF-mediated chromatin domains and downregulated LATS target gene expression.
2020-03-09 | GSE114319 | GEO
Project description:p53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator.
2015-12-11 | GSE74493 | GEO
Project description:Development of an improved inhibitor of Lats Kinases to promote regeneration of mammalian organs
| PRJNA804393 | ENA
Project description:The YAP/Hippo pathway is a key regulator of organ growth and size regulation and is involved in safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. We report on the gene expression changes associated with YAP activation by the selective small molecule LATS kinase inhibitor NIBR-LTSi in mouse intestinal organoids. We show that, LATS-LTSi activates YAP signalling, promotes proliferation, induces a regenerative phenotype and blocks differentiation.
2024-03-07 | GSE240969 | GEO
Project description:Perturbation of the tightly regulated dynamic process of cell fate underlies many human diseases. The molecular mechanisms regulating breast cell fate in the hierarchically organized luminal and basal lineages of breast epithelium remain largely elusive. We performed a high-content confocal image-based shRNA screen for regulators of primary human breast cell fate. Inhibition of the Hippo kinases LATS was found to promote luminal fate and increase the number of progenitors, which is a paradox given that Hippo effectors YAP/TAZ have been associated with basal fate. Mechanistically, LATS loss increases the activities of YAP/TAZ and ERα, which in concert control breast cell fate via intrinsic and paracrine effects. Reduced LATS expression is found in breast cancers with a poor prognosis; this diminishes the sensitivity of ERα-positive- and increases the sensitivity of ERα-negative cancers to endocrine therapy. Thus, in this study we have unraveled crosstalk between Hippo and estrogen signaling and shown that LATS loss triggers expansion of luminal progenitors, the highly suspected cell-of-origin in most breast cancers. In this dataset, we provide microarray gene expression analysis of normal breast epithelial cells, freshly dissociated from reduction mammoplasties, in which LATS1/2 were knocked down comparing it to non-targeting control expressing breast cells.
2017-01-27 | GSE61297 | GEO
Project description:Proviral integration site for Moloney murine leukemia virus (PIM) kinases promote human T helper 1 cell differentiation
| PRJNA174342 | ENA
Project description:The Hippo pathway plays a key role in development, organ size control, and tissue homeostasis, and its dysregulation contributes to cancer. The LATS tumor suppressor kinases phosphorylate and inhibit the YAP/TAZ transcriptional co-activators to suppress gene expression and cell growth. Through a screen of marine natural products, we identified microcolin B (MCB) as a Hippo activator. Structure-activity optimization yielded more potent MCB analogs, which led to identification of PITP as the direct molecular targets. We established a critical role of PITP in regulating LATS and YAP. Moreover, we showed that PITP influences the Hippo pathway via cellular PI4P. This study uncovers a previously unrecognized role of PITP in Hippo pathway regulation and as potential cancer therapeutic targets.
2022-03-20 | GSE198890 | GEO
Project description:Downregulation of p53 drives autophagy during human trophoblast differentiation
| PRJNA385332 | ENA