Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome of MEFs with BMP2 and DNA damage reagents

ABSTRACT: The tightly controlled BMP-Smad1 pathway is essential for embryonic development and postnatal tissue homeostasis. Dysfunction of BMP-Smad1 signaling also leads to tumor development such as juvenile polyposis and Cowden syndromes and various tumors in mouse models, with unknown pathological mechanisms. Here we establish a link between the BMP-Smad pathway and the prominent tumor suppressor Atm-p53 pathway. We identify activated nuclear Smad1 as an Atm substrate under genotoxic stress. Atm-mediated Smad1 S239 phosphorylation disrupts Smad1 interaction with protein phosphatase PPM1A and enhances Smad1 activation and up-regulation, which not only turns on target genes including Cdk1nc but also interacts with p53 and inhibits Mdm2-mediated p53 ubiquitination, leading to p53 stabilization. Functionally, Smad1 acts like a tumor suppressor in DNA damage response, cell transformation and tumorigenesis in a p53-dependent manner. Sequencing of the gastric cancer samples revealed that Smad1 is frequently mutated, with S239 as mutational hotspot. This study thus establishes the BMP-Smad1 pathway as an integral part of DNA damage response, which can suppresses tumorigenesis via p53. Transformed MEFs (Smad1f/f, Smad1f/f Cre) treated with 50ng/ml BMP2, 1 ug/ml doxorubincin, or both for different periods of time. The mRNA levels of all genes were compared using microarray analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Shuet Theng Lee

PROVIDER: E-GEOD-36843 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome of MEFs with BMP2 and DNA damage reagents

Project description:The tightly controlled BMP-Smad1 pathway is essential for embryonic development and postnatal tissue homeostasis. Dysfunction of BMP-Smad1 signaling also leads to tumor development such as juvenile polyposis and Cowden syndromes and various tumors in mouse models, with unknown pathological mechanisms. Here we establish a link between the BMP-Smad pathway and the prominent tumor suppressor Atm-p53 pathway. We identify activated nuclear Smad1 as an Atm substrate under genotoxic stress. Atm-mediated Smad1 S239 phosphorylation disrupts Smad1 interaction with protein phosphatase PPM1A and enhances Smad1 activation and up-regulation, which not only turns on target genes including Cdk1nc but also interacts with p53 and inhibits Mdm2-mediated p53 ubiquitination, leading to p53 stabilization. Functionally, Smad1 acts like a tumor suppressor in DNA damage response, cell transformation and tumorigenesis in a p53-dependent manner. Sequencing of the gastric cancer samples revealed that Smad1 is frequently mutated, with S239 as mutational hotspot. This study thus establishes the BMP-Smad1 pathway as an integral part of DNA damage response, which can suppresses tumorigenesis via p53.

2012-12-31 | GSE36843 | GEO

Expression signature in a human colorectal cancer cell lines, HCT116 and RKO, transfected with miR-101

Project description:Understanding of molecular system how tumor-suppressor p53 selectively activates and/or completes appropriate tumor-suppressor pathway in response to various stresses is still one of the most important issues to be clarified. We analyzed a molecular mechanism for the completion of p53-dependent ribosome stress responsible pathway by miR-101. To this end, expression microarray analyses were conducted in the presence or absence of miR-101. We found that miR-101 induces the activation of p53-dependent G2 phase cell cycle arrest through the increased phosphorylation of ATM, leading to the p53-depdent apoptosis.

2017-08-16 | GSE85696 | GEO

Comparsion of Smad1 and Smad5 Dependent Transcript Profiles in Zebrafish

Project description:The BMP signaling pathway regulates multiple steps of hematopoiesis, mediated through receptor-regulated Smads, including Smad1 and Smad5. Here we use loss-of-function approaches in zebrafish to compare the roles of Smad1 and Smad5 during embryonic hematopoiesis. Microarray experiments revealed that the two proteins regulate redundantly the key initiators of the hemato-vascular program, including scl, lmo2, and gfi1. However, each also regulates a remarkably distinct genetic program, with Smad5 uniquely regulating the BMP signaling pathway itself. Our results suggest that specificity of BMP signaling output, with respect to hematopoiesis, can be explained by differential functions of Smad1 and Smad5. Keywords: Gene expression transcript profiles

2008-08-22 | GSE8903 | GEO

Downregulation of LATS kinases alters p53 to promote cell migration

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

Stage-specific sensitivity to p53 restoration in lung cancer: cell line data

Project description:Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumor-suppressor pathways. The quest to personalize cancer medicine based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumor suppressors and activation of oncogenes are required for tumor maintenance. Mutations in the p53 tumor-suppressor pathway are a hallmark of cancer and significant efforts toward pharmaceutical reactivation of mutant p53 pathways are underway1-3. Here we show that restoration of p53 in established murine lung tumors leads to significant but incomplete tumor cell loss specifically in malignant adenocarcinomas but not in adenomas. Also, we define amplification of MAPK signaling as a critical determinant of malignant progression. The differential response to p53 restoration depends on activation of the Arf tumor suppressor downstream of hyperactive MAPK signaling. We propose that p53 naturally limits malignant progression by responding to increased oncogenic signaling, but is unresponsive to low levels of oncogene activity that are sufficient for early stages of lung tumor development. These data suggest that restoration of pathways important in tumor progression, as opposed to initiation, may lead to incomplete tumor regression due to the stage-heterogeneity of tumor cell populations. 3 cell lines each treated with Tamoxifen or EtOH vehicle. Tamoxifen treatment results in reactivation of p53 expression

2010-11-24 | E-GEOD-23873 | biostudies-arrayexpress

Expression data of human umbilical vein endothelial cells (HUVECs) treated with BMP-6 and BMP-9

Project description:Smad1/5 are transcription factors that engage in BMP-induced transcription. We determined and analyzed Smad1/5 binding sites by ChIP-sequencing. We used expression microarrays to compare the Smad1/5 binding sites identified by ChIP-seq to BMP-induced gene expressions. HUVECs were treated with BMP for RNA extraction and hybridization on Affymetrix microarrays.

2011-07-15 | E-GEOD-27631 | biostudies-arrayexpress

Global and p53-dependent transcriptional response of fibroblasts to Klebsiella pneumoniae

Project description:Increasing evidence highlights the role of bacteria in the physiopathology of cancer. However, the underlying molecular mechanisms remains poorly understood. Several cancer-associated bacteria have been shown to produce toxins which modulate the tumor suppressor p53 and thereby interfere with the host defense against tumorigenesis. Here, we show that lipopolysaccharides from Klebsiella pneumoniae (Kp) strongly inhibit the host p53 pathway and impairs p53 transcriptional activity upon DNA damage and oncogenic stress, preventing its tumor suppressive function.

2022-02-26 | GSE174531 | GEO

Stage-specific sensitivity to p53 restoration in lung cancer: tumor data

Project description:Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumor-suppressor pathways. The quest to personalize cancer medicine based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumor suppressors and activation of oncogenes are required for tumor maintenance. Mutations in the p53 tumor-suppressor pathway are a hallmark of cancer and significant efforts toward pharmaceutical reactivation of mutant p53 pathways are underway1-3. Here we show that restoration of p53 in established murine lung tumors leads to significant but incomplete tumor cell loss specifically in malignant adenocarcinomas but not in adenomas. Also, we define amplification of MAPK signaling as a critical determinant of malignant progression. The differential response to p53 restoration depends on activation of the Arf tumor suppressor downstream of hyperactive MAPK signaling. We propose that p53 naturally limits malignant progression by responding to increased oncogenic signaling, but is unresponsive to low levels of oncogene activity that are sufficient for early stages of lung tumor development. These data suggest that restoration of pathways important in tumor progression, as opposed to initiation, may lead to incomplete tumor regression due to the stage-heterogeneity of tumor cell populations. 18 tumors of different grade and treatment status. 6 treated grade 3, 4 treated grade2, 4 untreated grade3, 4 untreated grade2

2010-11-24 | E-GEOD-23874 | biostudies-arrayexpress

Expression data of human pulmonary arterial smooth muscle cells (PASMCs) treated with BMP-4

Project description:Smad1/5 are transcription factors that engage in BMP-induced transcription. We determined and analyzed Smad1/5 binding sites by ChIP-sequencing. We used expression microarrays to compare the Smad1/5 binding sites identified by ChIP-seq to BMP-induced gene expressions. PASMCs were treated with 50 ng/ml BMP-4 for 0, 2, or 24 hrs. RNA was extracted and hybridized on Affymetrix microarrays.

2011-07-15 | E-GEOD-28847 | biostudies-arrayexpress

SMAD1/5 binding regions of human pulmonary arterial smooth muscle cells (PASMCs) treated with BMP

2011-07-16 | GSE28848 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data