E-GEOD-57133
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA245533PRJNA203655PRJNA245832
PROVIDER: E-GEOD-57133 | ExpressionAtlas | 2015-08-04
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-57133-analysis-methods.tsv | Tabular | |||
| E-GEOD-57133-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-57133-configuration.xml | Xml | |||
| E-GEOD-57133-percentile-ranks.tsv | Tabular | |||
| E-GEOD-57133.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 86 |
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Project description:ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [expression]
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Project description:ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [ChIP-seq]
| PRJNA245832 | ENA
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
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
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’s 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.
2015-03-05 | GSE57177 | GEO
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’s 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.
2015-03-05 | GSE57133 | GEO
Project description:ERBB2 is an oncogenic driver with frequent gene mutations and amplification in human lung tumors and is an attractive target for lung cancer therapy. However, target therapies can be improved by understanding the in vivo mechanisms regulated by ERBB2 during lung tumor development. Here, we generated genetic mouse models to show that Erbb2 loss inhibited lung tumor development induced by deletion of Pten and Smad4. Transcriptome analysis showed that Erbb2 loss suppressed the significant changes of most of the induced genes by ablation of Pten and Smad4. Overlapping with ERBB2-associated human lung cancer genes further identified those ERBB2 downstream players potentially conserved in human and mouse lung tumors. Furthermore, MED24 was identified as a crucial oncogenic target of ERBB2 in lung tumor development. Taken together, ERBB2 is required for the dysregulation of cancer-related genes, such as MED24, during lung tumor development.
2019-06-19 | GSE128620 | GEO
Project description:The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Loss of SMAD4 is a key event in late-stage CRC resulting in the progression to metastatic CRC in 10-30% of the cases. However, the biological processes and underlying molecular mechanisms that it affects are not fully understood. Here, we applied a multi-omics approach to a CRC tumor progression organoid model that faithfully reflects the metastasis-inducing effects of SMAD4 inactivation. We show that loss of SMAD4 results in loss of differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFB, WNT, and VEGF pathways. In addition, SMAD4 inactivation leads to increased secretion of proteins that are known to be involved in a variety of pro-metastatic processes. Finally, we show that one of the factors that is specifically secreted by metastatic organoids – DKK3 – reduces the anti-tumor effects of natural killer cells (NKCs). Altogether, our data provides promising new targets concerning the role of SMAD4 perturbation and metastatic disease in CRC.
2022-12-11 | PXD036441 | Pride
Project description:Over 85% of lung cancer patients harbor overt or subclinical metastases at diagnosis, and therefore most patients die of progressive metastatic disease despite aggressive local and systemic therapies. Somatic mutations in the Smad4 gene have been found in non-small-cell lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generated a highly aggressive lung cancer mouse model bearing conditional KrasG12D, p53fl/fl LOF and/or Smad4 fl/fl LOF mutations. The Smad4fl/fl; p53 fl/fl; KrasG12D (SPK) mutant mice manifested a much higher incidence of tumor metastases than the p53 fl/fl; KrasG12D (PK) mice. Molecularly, PAK3 was identified as a novel downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice was achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3’UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components suggests clinical use of Smad4 LOF as a potential marker for prognosis in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.
2021-05-07 | GSE164436 | GEO
Project description:In the current work, we add to the understanding of differentiated-cell-derived tumorigenesis by demonstrating that simultaneous loss of SMAD4 and activation of the WNT pathway triggers stem cell properties and adenoma formation in the differentiated epithelium. Under normal conditions, SMAD4 loss does not immediately affect the normal tissue homeostasis in the intestine. However, after approximately 6 months, adenomas will develop and feature elevated WNT signaling, suggesting that SMAD4 loss predisposes to WNT-driven tumors. Interestingly, ectopic elevation of WNT in the context of a SMAD4 mutant background triggers stem cell activity and adenoma formation in the differentiated epithelium. Thus Smad4 functions to suppress villus cells from re-entering the cell cycle and functioning as stem cells upon exposure to high levels of WNT. Thus, we report a new mechanism through which differentiated cells can contribute to tumor formation.
2018-07-23 | GSE102171 | GEO