Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA562114 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10037966_1.fastq.gz | Fastqsanger.gz | |||
| SRR10037966_2.fastq.gz | Fastqsanger.gz | |||
| SRR10037967_1.fastq.gz | Fastqsanger.gz | |||
| SRR10037967_2.fastq.gz | Fastqsanger.gz | |||
| SRR10037968_1.fastq.gz | Fastqsanger.gz |
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Project description:Uncontrolled Transforming growth factor-beta (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGFβ-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGFβ-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGFβ, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGFβ signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGFβ repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGFβ signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (TAZ/YAP), the TEAD family of transcription factors (TEAD1/2/3/4), or the TGFb signaling pathway (with SB-431542, an inhibitor of the TBRI recpeptor) in human MDA-MB-231-LM2 breast cancer cells treated with TGFβ1. Human MDA-MB-231-LM2-4 breast cancer cells were transfected with control siRNA, or siRNAs targeting TAZ/YAP or all four TEADs and were treated 24 hours later with 500pM TGFβ1 or 5mM SB-431542 for an additional 24 hours. Total RNA was isolated and twelve microarrays in total were performed, with each condition carried out three times on separate days. The Boston University Microarray Core generated the data using the Affymetrix Human Gene 1.0 St Array.
2014-04-02 | E-GEOD-56445 | biostudies-arrayexpress
Project description:TAZ, one of the key components of Hippo signaling pathway, is a transcription coactivator and plays an important role in cell proliferation, anti-apoptosis, therapeutic resistance, cancer stemness and tumorigenesis. TAZ mediated transcription program through transcription factors, such as TEAD family members. Genome-wide TAZ occupancy is poorly defined. Here, using a tet-inducible TAZ activation in mammary epithelial MCF10A cells, we characterized genome-wide binding sites in different TAZ activation time points. We found vast majority of TAZ binds to distal enhancer and intergenic regions of genes in the early TAZ activation time point and shift to promoter regions in the later TAZ activation time point. We identified three distinctive TAZ binding patterns to its targets. Furthermore, we found TAZ activation results in chromatin architecture alterations. Our studies provide insight of TAZ regulated transcription program in mammary epithelial cells and indicate potential therapeutic targets for breast cancer.
2023-10-16 | GSE240244 | GEO
Project description:TAZ, one of the key components of Hippo signaling pathway, is a transcription coactivator and plays an important role in cell proliferation, anti-apoptosis, therapeutic resistance, cancer stemness and tumorigenesis. TAZ mediated transcription program through transcription factors, such as TEAD family members. Genome-wide TAZ occupancy is poorly defined. Here, using a tet-inducible TAZ activation in mammary epithelial MCF10A cells, we characterized genome-wide binding sites in different TAZ activation time points. We found vast majority of TAZ binds to distal enhancer and intergenic regions of genes in the early TAZ activation time point and shift to promoter regions in the later TAZ activation time point. We identified three distinctive TAZ binding patterns to its targets. Furthermore, we found TAZ activation results in chromatin architecture alterations. Our studies provide insight of TAZ regulated transcription program in mammary epithelial cells and indicate potential therapeutic targets for breast cancer.
2023-10-16 | GSE240241 | GEO
Project description:TAZ, one of the key components of Hippo signaling pathway, is a transcription coactivator and plays an important role in cell proliferation, anti-apoptosis, therapeutic resistance, cancer stemness and tumorigenesis. TAZ mediated transcription program through transcription factors, such as TEAD family members. Genome-wide TAZ occupancy is poorly defined. Here, using a tet-inducible TAZ activation in mammary epithelial MCF10A cells, we characterized genome-wide binding sites in different TAZ activation time points. We found vast majority of TAZ binds to distal enhancer and intergenic regions of genes in the early TAZ activation time point and shift to promoter regions in the later TAZ activation time point. We identified three distinctive TAZ binding patterns to its targets. Furthermore, we found TAZ activation results in chromatin architecture alterations. Our studies provide insight of TAZ regulated transcription program in mammary epithelial cells and indicate potential therapeutic targets for breast cancer.
2023-10-16 | GSE240237 | GEO
Project description:Cancer development and progression depend on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Despite the identification of the plasticity of adipocytes, the primary breast stromal cells, both in physiology and cancer, we lack a complete understanding of mechanisms that regulate adipocyte-tumor cell crosstalk. Here we dissected the breast cancer crosstalk with adipocytes and studied relevant molecules. We identified that the ability of breast cancer cells to dedifferentiate adipocytes is intrinsic subtype-dependent, with all breast cancer subtypes, except for HER2+ER+ subtype, capable of inducing this phenomenon. Crosstalk between breast cancer cells and adipocytes in vitro increased cancer stem-like features and recruitment of pro-tumorigenic immune cells, through chemokine production. Serum amyloid A1 (SAA1) was in vitro identified as a regulator of the adipocyte dedifferentiation program in triple-negative breast cancer (TNBC) through CD36 and P2XR7 signaling. In human TNBCs, SAA1 expression was associated with CAA infiltration, inflammation, stimulated lipolysis, stem-like properties and distinct tumor immune microenvironment. Our findings provide evidence that interaction between tumor cells and adipocytes through SAA1 release is relevant to the aggressiveness of TNBC, potentially supporting its targeting.
2024-01-15 | PXD041186 | Pride
Project description:Here using mouse genetic models and human cancer cells, we show that YAP/TAZ reprogram polyamine metabolism to promote cell proliferation and tumor growth. Mechanistically, YAP/TAZ increases polyamine synthesis mainly through direct upregulation of the major rate-limiting enzyme ornithine decarboxylase 1. We further demonstrate that the polyamine spermidine sustains eukaryotic translation factor 5A (eIF5A) hypusination to support efficient translation of histone demethylase LSD1 that maintains a favored epigenetic status for YAP/TAZ-induced cell proliferation. Furthermore, inhibiting either polyamine synthesis or LSD1 can suppress YAP/TAZ-induced cell proliferation in mouse liver and human cancer cells. Thus our study identifies a YAP/TAZ-polyamine-eIF5A hypusination-LSD1 axis as required for YAP/TAZ-induced cell proliferation and tumor growth and suggests LSD1 as a critical target of polyamine in tumorigenesis.
2022-01-01 | GSE176329 | GEO
Project description:Here using mouse genetic models and human cancer cells, we show that YAP/TAZ reprogram polyamine metabolism to promote cell proliferation and tumor growth. Mechanistically, YAP/TAZ increases polyamine synthesis mainly through direct upregulation of the major rate-limiting enzyme ornithine decarboxylase 1. We further demonstrate that the polyamine spermidine sustains eukaryotic translation factor 5A (eIF5A) hypusination to support efficient translation of histone demethylase LSD1 that maintains a favored epigenetic status for YAP/TAZ-induced cell proliferation. Furthermore, inhibiting either polyamine synthesis or LSD1 can suppress YAP/TAZ-induced cell proliferation in mouse liver and human cancer cells. Thus our study identifies a YAP/TAZ-polyamine-eIF5A hypusination-LSD1 axis as required for YAP/TAZ-induced cell proliferation and tumor growth and suggests LSD1 as a critical target of polyamine in tumorigenesis.
2022-01-01 | GSE174041 | GEO
Project description:Tuft cells restrain pancreatic tumorigenesis through paracrine eicosanoid signaling
| PRJNA645675 | ENA
Project description:TAZ, a key component in Hippo pathway, plays an important role in breast tumorigenesis. To understand the entrisic as well as extrinsic role of TAZ in mammary tumors, we performed RNA-seq analysis using mammary tumors generated from sgControl or sgTaz 4T1 cells.
2023-05-31 | GSE205160 | GEO
Project description:Background: Cancer metastasis is dependent on cell migration. Several mechanisms, including epithelial-to-mesenchymal transition (EMT) and actin fiber formation, could be involved in cancer cell migration. As a downstream effector of the Hippo signaling pathway, transcriptional coactivator with PDZbinding motif (TAZ) is recognized as a key mediator of the metastatic ability of breast cancer cells. We aimed to examine whether TAZ affects the migration of breast cancer cells through the regulation of EMT or actin cytoskeleton. Methods: MCF-7 and MDA-MB-231 cells were treated with siRNA to attenuate TAZ abundance. Transwell migration assay and scratch wound healing assay were performed to study the effects of TAZ knockdown on cancer cell migration. Fluorescence microscopy was conducted to examine the vinculin and phalloidin. Semiquantitative immunoblotting and quantitative real-time PCR were performed to study the expression of small GTPases and kinases. Changes in the expression of genes associated with cell migration were examined through next-generation sequencing. Results: TAZ-siRNA treatment reduced TAZ abundance in MCF-7 and MDA-MB- 231 breast cancer cells, which was associated with a significant decrease in cell migration. TAZ knockdown increased the expression of fibronectin, but it did not exhibit the typical pattern of EMT progression. TGF-b treatment in MDA-MB-231 cells resulted in a reduction in TAZ and an increase in fibronectin levels. However, it paradoxically promoted cell migration, suggesting that EMT is unlikely to be involved in the decreased migration of breast cancer cells in response to TAZ suppression. RhoA, a small Rho GTPase protein, was significantly reduced in response to TAZ knockdown. This caused a decrease in the expression of the Rho-dependent downstream pathway, i.e., LIM kinase 1 (LIMK1), phosphorylated LIMK1/2, and phosphorylated cofilin, leading to actin depolymerization. Furthermore, myosin light chain kinase (MLCK) and phosphorylated MLC2 were significantly decreased in MDA-MB-231 cells with TAZ knockdown, inhibiting the assembly of stress fibers and focal adhesions. Conclusion: TAZ knockdown inhibits the migration of breast cancer cells by regulating the intracellular actin cytoskeletal organization. This is achieved, in part, by reducing the abundance of RhoA and Rho-dependent downstream kinase proteins, which results in actin depolymerization and the disassembly of stress fibers and focal adhesions.
2024-04-27 | GSE264547 | GEO