Gene Transcriptional Variation of Hepatic Progenitor Cells after TGF-훽1-Induced EMT Transition and EGF-Induced MET Reversion
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA698358 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TGF-b1 induces hepatic progenitor cells experience an epithelial-mesenchymal transition, and EGF could reverse this process via mesenchymal-epithelial transition. Yet, the mechanism underline these EMT and MET processes are not clear. The aim of this study is to reveal the genes with significant difference during these EMT and MET process in hepatic progenitor cells.
2021-04-23 | GSE165858 | GEO
Project description:NMuMG is an epithelial cell line that can be induced into EMT by TGF-β treatment or MET by TGF-β withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype. Transcription factors that are regulated during EMT and its reverse process MET are candidate genes for the regulations of the EMT marker genes.
2013-07-26 | GSE48204 | GEO
Project description:NMuMG is an epithelial cell line that can be induced into EMT by TGF-β treatment or MET by TGF-β withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype. Transcription factors that are regulated during EMT and its reverse process MET are candidate genes for the regulations of the EMT marker genes. NMuMG cells treated with vehicle, TGF-β for 11 days, or 11days of TGF-β treatment followed by TGF-β withdrawl for another 13 days. RNA from these 3 conditions of NMuMG were extracted and subject to microarray analysis
2013-07-26 | E-GEOD-48204 | biostudies-arrayexpress
Project description:Tumors and tumor surrounding tissues produce multiple growth factors that influence tumor cell behavior via different signal transduction pathways. Growth factors like transforming growth factor beta (TGFβ) and epidermal growth factor (EGF) were shown to induce proliferation, migration and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of TGFβ, EGF and the combination of both factors on A549 cells. Both factors stimulated A549 migration to a similar extent but with a different kinetic and the combination had an additive effect. While EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway, this pathway was dispensable for TGFβ-induced migration despite a strong activation by TGFβ. Proteome analysis revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF but only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, EGF was unable to increase invasion of A549 cells on its own and failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF may partly compensate each other for stimulation of cell migration but abrogation of TGFβ signaling may be more suitable for antagonizing invasion.
2021-04-08 | PXD023024 | Pride
Project description:This file contains a 136-node modular Boolean network model of EMT triggered by biomechanical and growth signaling crosstalk, linked to a published network of epithelial contact inhibition, proliferation, and apoptosis (MODEL2006170001). This model reproduces the ability of the core EMT transcriptional network to maintain distinct epithelial, hybrid E/M and mesenchymal states, as well as EMT driven by mitogens such as EGF on stiff ECM. We also reproduce the observed lack of stepwise MET, in that our model's dynamics does not pass through the hybrid E/M state during MET. We show that in the absence of strong autocrine signals such as TGFβ (not included in this version), cells cannot maintain their mesenchymal state in the absence of mitogens, on softer matrices, or at high cell density.
2023-12-13 | MODEL2208050001 | BioModels
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225688 | GEO
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225687 | GEO
Project description:We performed single-cell RNA-sequencing (scRNA-seq) to elucidate osteoblastic transcriptional programs during zebrafish caudal fin regeneration. We show that osteoprogenitors are enriched with components associated with epithelial-to-mesenchymal transition (EMT) and its reverse, mesenchymal-to-epithelial transition (MET). Trajectory analyses indicate osteoblastic cells solely expressed EMT components, or transiently expressed components for MET before EMT. We provide evidence that the EMT markers cdh11 and twist2 are co-expressed in dedifferentiating cells at the amputation stump, and in differentiating osteoblastic cells in the regenerate, the latter of which are enriched in EMT signatures. We also show that esrp1, a regulator of alternative splicing in epithelial cells that is associated with MET, is expressed in a subset of osteoprogenitors during outgrowth. This study provides a single cell resource for the study of osteoblastic cells during zebrafish fin regeneration, and supports the contribution of MET- and EMT-associated components to this process.
2021-12-27 | GSE192498 | GEO
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225690 | GEO
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225689 | GEO