TEAD1 ChIP-seq on on MDA-MB-231 and Detroit X1 562 cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA587718 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10401927.fastq.gz | Fastqsanger.gz | |||
| SRR10401928.fastq.gz | Fastqsanger.gz | |||
| SRR10401929.fastq.gz | Fastqsanger.gz | |||
| SRR10401930.fastq.gz | Fastqsanger.gz | |||
| SRR10401931.fastq.gz | Fastqsanger.gz |
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Project description:The Hippo Pathway is a critical signaling network that regulates organ size and cellular proliferation in metazoans. The transcriptional enhanced associate domain (TEAD) family of transcription factors serve as the receptors for the downstream effectors of the Hippo pathway, YAP and TAZ, to upregulate expression of multiple genes involved in proliferation, cell-fate determination, polarity, and survival1. Recent work revealed that TEAD proteins are palmitoylated at a conserved cysteine with the lipid tail extending into the hydrophobic core of the protein2. Mutagenic and covalent modulation of the palmitoylation site disrupts Hippo signaling2,3; however, an understanding of why TEAD proteins require this seemingly essential modification and the therapeutic implications of modulating TEAD palmitoylation has remained elusive. Here we report the identification and optimization of a potent pan-TEAD small molecule that binds the TEAD lipid pocket (LP), blocks palmitoylation, and dysregulates TEAD activity in multiple cancer cell lines. Cellular and biochemical data interrogating the mechanism of action for our compound reveal TEAD palmitoylation to function as a checkpoint that regulates TEAD homeostasis. We show that bypassing this checkpoint with a small molecule increases TEAD protein levels thereby decreasing the ability of YAP/TAZ to activate downstream target gene transcription in a dominant-negative manner. Our study demonstrates a new role for lipidation in protein signaling and establishes the TEAD LP as a bona fide therapeutic site for modulation of the Hippo Pathway.
2020-06-03 | GSE139951 | GEO
Project description:A total of 432 genes were found to be differentially expressed in M1SF370 bacterial population internalized in Detroit 562 human pharyngeal cells when compared with the same strain incubated in the absence of Detroit 562 cells. While most of them (349/432 i.e. 80.8%) were up regulated, 83 genes were down regulated contributing to 19.2% of the total differentiated genes. The major contributor of the latter category was phage-related genes (35 genes). Almost ¼ of these genes (106) belonged to a category of Unknown or possible predicted function. Most notably, up-regulated genes belonged to amino acid transport , cell division, cell envelope biogenesis, DNA replication correlated well with up-regulated 67 genes belonged to translation and ribosomal structure. Further, up-regulation of 12/15 virulence-related genes indicated that human host cell internalized bacteria are highly virulent as compared to laboratory grown culture in test-tubes.
2011-06-10 | GSE27846 | GEO
Project description:A total of 432 genes were found to be differentially expressed in M1SF370 bacterial population internalized in Detroit 562 human pharyngeal cells when compared with the same strain incubated in the absence of Detroit 562 cells. While most of them (349/432 i.e. 80.8%) were up regulated, 83 genes were down regulated contributing to 19.2% of the total differentiated genes. The major contributor of the latter category was phage-related genes (35 genes). Almost ¼ of these genes (106) belonged to a category of Unknown or possible predicted function. Most notably, up-regulated genes belonged to amino acid transport , cell division, cell envelope biogenesis, DNA replication correlated well with up-regulated 67 genes belonged to translation and ribosomal structure. Further, up-regulation of 12/15 virulence-related genes indicated that human host cell internalized bacteria are highly virulent as compared to laboratory grown culture in test-tubes. S. pyogenes strain type M1 SF370 (wild-type) was procured from ATCC (ATCC 700294). Detroit 562 pharyngeal cells were obtained from ATCC and maintained in MEM with 10% FBS in humidified CO2-incubator. Purified cDNA preparations from the Detroit cells-internalized bacteria and that were cultured without Detroit cells, were labeled with either Alexafluor-555 or Alexafluor-647 depending on the experimental design ( i.e. dye swap experiment). Differentially labeled probes were then combined and purified. Using four independently isolated RNA preparations (biological replicates), a total of 8 experiments (incorporating 4 dye swaps) were performed. Accordingly eight hybridization measurements for this mutant were obtained. Exp-1 and -2 (GSM687276, GSM687310-dye swap) are the technical replicates of the biological sample-1, Exp-3 and -4 (GSM687311, GSM687312-dye swap) are technical replicates of biological sample-2, Exp-5 and -6, (GSM687313,GSM687319-dye swap,) are technical replicates of the biological sample-3, and finally Exp-7 and -8, (GSM687320,GSM687321-dye swap) are technical replicates of the biological sample-4. .
2011-06-10 | E-GEOD-27846 | biostudies-arrayexpress
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| S-ECPF-GEOD-20085 | biostudies-other
Project description:Single clones were isolated from the Detroit 562 cell line and implanted into NOD/SCID mice to determine whether clonal populations within one cell line had fuctionally distinct phenotypes, in the form of differing tumour initiating activity. From these data I found that different clonal populations had different tumour initiating activity, which lead to this investigation as to whether these functionally distinct populations were also genetically distinct.
2010-01-22 | GSE19994 | GEO
Project description:In the past decades, altered Follistatin‑like 1 (FSTL1) expression has been documented in a variety of cancers, while its functional roles are poorly understood. Particularly in breast cancer, the expression of FSTL1 and its signaling pathway remain to be determined. In the present study, an elevated FSTL1 expression and a supressed cell proliferation were detected in a specific brain metastatic cell line MDA‑MB‑231‑BR (231‑BR), compared with its parental cell line MDA‑MB‑231. However, this protein was hardly detected in the other three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1 specific shRNAs were used to overexpress or knock down FSTL1 in MDA‑MB‑231 or 231‑BR, respectively (MDA‑MB‑231FSTL1 or 231‑BRsh FSTL1). Results showed that overexpression of FSTL1 inhibited MDA‑MB‑231 cell proliferation, while knockdown of FSTL1 in 231‑BR cells promotes cell proliferation, compared with their corresponding control groups. These results were further confirmed in nude mouse xenografts. The tumor volume in 231‑BR cell-bearing mice was significantly smaller than that of MDA‑MB‑231 group, and reduction of tumor volume was detected in MDA‑MB‑231FSTL1 cell-bearing mice compared with the control group. Previous studies revealed that TGF‑β-Smad2/3 signaling pathway was activated in 231‑BR and MDA‑MB‑231FSTL1 cells, which may contribute to the inhibited cell proliferation. In addition, Smad3 knockdown could restore the inhibition of cell proliferation induced by FSTL1 overexpression in MDA‑MB‑231FSTL1 cells, indicating that the anti‑proliferative effect of FSTL1 overexpression may be associated with Smad3 involved TGF‑β signaling pathway regulation. This study identified FSTL1 as an inhibitor of cell proliferation in MDA‑MB‑231 and 231‑BR cell lines, which may provide new insights into the development and management of breast cancer.
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