Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling

ABSTRACT: We have reported previously that in preclinical models, BMP4 is a potent inhibitor of breast cancer metastasis and that high BMP4 protein levels predict favourable patient outcome. Here, we investigated the requirement for functional SMAD4 in mediating the anti-metastatic response of BMP4, given reports of promotion of metastasis by BMP4 in cancers where SMAD4 is frequently deleted. BMP4-induced inhibition of metastasis does not require functional SMAD4 in tumor cells. However, tumor cell intrinsic signalling using a constitutively active BMP receptor does require functional SMAD4 to suppress metastasis, thus implicating BMP4 mediated paracrine signalling as a contributor to the inhibition of metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199628 | GEO | 2024/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effect of BMP4 and noggin on gene expression in murine R1 ES cells

Project description:To confirm that the SMAD1/5- and SMAD4-associated genes are direct transcriptional regulators in mESCs in response to BMP, we treated undifferentiated R1 ES cells with BMP4 or with the BMP4 antagonist noggin, which can inhibit BMP signaling effectively for 4 h. Undifferentiated R1 ES cells were treated for 4 h with BMP4 or with the BMP4 antagonist noggin, which can inhibit BMP signaling effectively. Untreated R1 ES cells served as the control.

2010-03-07 | E-GEOD-20527 | biostudies-arrayexpress

IMR32-BMP4

Project description:Growth suppressing Wnt/BMP4-Msx/Notch signalling in neuroblastoma

| PRJEB36530 | ENA

Effect of BMP4 and noggin on gene expression in murine R1 ES cells

2010-03-01 | GSE20527 | GEO

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [expression]

Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1 expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer. The microarray data includes two different ages of mouse lung samples. The microarray for the study on late stage was did on 12-month-old wild type mouse lungs and Ptend/dSmad4d/d mouse lung tumors. This study was used to identify the significantly changed genes between lung tumors and wild type lungs. The microarray for the study on early stage was did on 7-month-old wild type, Ptend/d and Ptend/dSmad4d/d mouse lungs. This study was used to identify the significantly changed driven genes before the lung tumor initiation and metastasis.

2015-03-05 | E-GEOD-57133 | biostudies-arrayexpress

Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours

Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.

2014-06-01 | E-GEOD-51632 | biostudies-arrayexpress

Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes [array]

Project description:Airway remodelling in chronic obstructive pulmonary disease (COPD) originates, in part, from smoking-induced changes in airway basal stem/progenitor cells (BCs). Based on the knowledge that bone morphogenetic protein 4 (BMP4) influences epithelial progenitor function in the developing and adult mouse lung, we hypothesised that BMP4 signalling may regulate the biology of adult human airway BCs relevant to COPD. BMP4 signalling components in human airway epithelium were analysed at the mRNA and protein levels, and the differentiation of BCs was assessed using the BC expansion and air-liquid interface models in the absence/presence of BMP4, BMP receptor inhibitor and/or small interfering RNAs against BMP receptors and downstream signalling.

2020-05-28 | GSE128708 | GEO

Circulating endoglin induces hypertension via the upregulated expression of BMP4

Project description:Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and often associated with increased levels of sEng. Although a pathogenic role for sEng involving hypertension has been reported in several animal models of preeclampsia, the exact molecular mechanisms implicated remain to be identified. To search for sEng-induced mediators, we have analyzed the protein secretome of human endothelial cells in the presence of sEng. We find that sEng induces the expression of BMP4 in endothelial cells, as evidenced by their proteomic signature, gene transcript levels and BMP4 promoter activity. A mouse model of preeclampsia with high sEng plasma levels (sEng+) showed increased levels of BMP4 transcripts in lungs and increased circulating BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appears 18 days after mating, precisely coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 are positively correlated in pregnant women with and without preeclampsia. Interestingly, sEng-induced arterial pressure elevation in sEng+ mice was abolished in the presence of the BMP4 inhibitor noggin, suggesting that BMP4 is a downstream mediator of sEng. These results provide a better understanding on the role of sEng in the pathobiology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.

2020-04-23 | PXD016228 | Pride

Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes [RNA-Seq]

2020-05-28 | GSE101353 | GEO

Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours

2014-06-01 | GSE51632 | GEO

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [ChIP-seq]

Project description:Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1M-bM-^@M-^Ys expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer. Examination of genome-wide SMAD4 binding in 7-month-old Ptend/d mouse lung.

2015-03-05 | E-GEOD-57177 | biostudies-arrayexpress

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