RNAi-mediated ablation of Nrf2 in PyMT-1099 LT, Py2T LT and MT∆Ecad mesenchymal breast cancer cells
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PROVIDER: PRJNA777587 | ENA |
REPOSITORIES: ENA
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Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. We have aimed at exploring the crosstalk between ROS and an EMT induced by TGFb in breast cancer cells. Methods: We observed that cells exposed to TGFb displayed a decrease of ROS levels. Furthermore, we identified an activation of the Nrf2 transcription factor, master regulator of the antioxidant response in TGFb-induced mesenchymal cells. In order to know the effect of Nrf2 ablation in epithelial and mesenchymal cells, RNAi-mediated ablation for Nrf2 was performed. Results: RNAi-mediated ablation of Nrf2 led to mesenchymal cancer cell death due to ferroptosis, an iron- and oxidative stress-dependent cell death. Moreover, analysis revealed that several glutathione pathway genes were specifically regulated by Nrf2, suggesting a role of glutathione-related pathways in mesenchymal cell survival. Conclusion: In this study we report the criticial role of the Nrf2-mediated glutathione metabolism in the protection of metastatic breast cancer cells from ferroptosis. Therapeutic targeting of antioxidant pathways may thus be beneficial for patients with metastatic disease.
2022-10-15 | GSE187478 | GEO
Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. However, several of the studies have been carried out using model systems that don’t appropriately recapitulate all stages of the dynamic process of EMT. Hence, there is a need to overcome this limitation by development of a model system that allows us to mimic each stage of EMT and accurately assess the plastic changes associated with it. Methods: We have derived a cancer cell line from the PyMT-MMTV model of breast cancer, named PyMT-1099 cells, and undertaken a detailed characterization of the morpho-genetic changes it undergoes during a TGF-induced EMT. Further, we have also performed high throughput transcriptomics on PyMT-1099 cells undergoing EMT in a high resolution kinetic of TGF treatment. Results: We show that PyMT-1099 cells undergo an EMT comparable to the classically used immortalized NMuMG cells as assessed by morphological, and marker expression changes on TGFtreatment. Further, PyMT-1099 cells can also migrate in vitro in response to TGF treatment. These cells are also tumorigenic and lead to metastasis formation when transplanted into immunocompromised mice. Conclusion: In this study we report the development of PyMT-1099 cells as an excellent tool to model and study breast cancer-associated EMT both in vitro and in vivo and show that these cells overcome the limitations posed by other cellular systems currently being used to study EMT
2018-10-03 | GSE114572 | GEO
Project description:Analysis of gene-expression alterations in primitive LT-HSCs as early as 2 days post sex steroid ablation. This study aimed to determine potential intrinsic changes occuring in the LT-HSC population associated with sex steroid ablation (SSA) at a timepoint that preceeded the earliest reported functional hematopoietic enhancements occuring at day 7 post SSA. These results are vital in providing insight into the role of LT-HSCs in initiating SSA-mediated immune regeneration. Total RNA obtained from BM-sorted LT-HSC 2 days after sex steroid ablation compared to sham sex steroid ablation controls.
2015-03-01 | E-GEOD-64841 | biostudies-arrayexpress
Project description:Analysis of gene-expression alterations in primitive LT-HSCs as early as 2 days post sex steroid ablation. This study aimed to determine potential intrinsic changes occuring in the LT-HSC population associated with sex steroid ablation (SSA) at a timepoint that preceeded the earliest reported functional hematopoietic enhancements occuring at day 7 post SSA. These results are vital in providing insight into the role of LT-HSCs in initiating SSA-mediated immune regeneration.
2015-03-01 | GSE64841 | GEO
Project description:PyMT-1099, a murine derived cell line is a breast cancer specific model for EMT
| PRJNA471818 | ENA
Project description:Pseudomonas stutzeri 1099 genome sequencing
| PRJNA695687 | ENA
Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. However, several of the studies have been carried out using model systems that don’t appropriately recapitulate all stages of the dynamic process of EMT. Hence, there is a need to overcome this limitation by development of a model system that allows us to mimic each stage of EMT and accurately assess the plastic changes associated with it. Methods: We have derived a cancer cell line from the PyMT-MMTV model of breast cancer, named PyMT-1099 cells, and undertaken a detailed characterization of the morpho-genetic changes it undergoes during a TGFbeta-induced EMT. Further, we have also performed high throughput transcriptomics on PyMT-1099 cells undergoing EMT in a high resolution kinetic of TGFbeta treatment. Results: We show that PyMT-1099 cells undergo an EMT comparable to the classically used immortalized NMuMG cells as assessed by morphological, and marker expression changes on TGFbeta treatment. Further, PyMT-1099 cells can also migrate in vitro in response to TGFbeta treatment. These cells are also tumorigenic and lead to metastasis formation when transplanted into immunocompromised mice. Conclusion: In this study we report the development of PyMT-1099 cells as an excellent tool to model and study breast cancer-associated EMT both in vitro and in vivo and show that these cells overcome the limitations posed by other cellular systems currently being used to study EMT
2018-10-03 | GSE117474 | GEO
Project description:An epithelial-mesenchymal transition (EMT) has been implicated in cancer metastasis, drug resistance, and in conferring stem cell-like traits to cancer cells. Most studies investigating EMT in cancer have either utilized immortalized or cancer cell lines that are already primed to undergo an EMT and do not adequately represent a fully differentiated epithelial state in the absence of an EMT induction. Hence, model systems are required which recapitulate all stages of EMT in cancer cells. Here, we report the derivation and characterization of epithelial PyMT-1099 cancer cells from the MMTV-PyMT mouse model of breast cancer. We demonstrate that PyMT-1099 cells undergo an EMT upon TGFβ treatment, while upon TGFβ withdrawal they go through a mesenchymal-epithelial transition (MET), as assessed by changes in cell morphology and marker expression and comparable to normal murine mammary gland NMuMG cells. However, in contrast to NMuMG cells, PyMT-1099 cells show an increase in cell migration and are highly tumorigenic and metastatic when transplanted into immunocompromised mice. Finally, we report cancer cell-specific changes in gene expression during EMT of PyMT-1099 cells not found in non-transformed NMuMG cells. Thus, PyMT-1099 cells are a versatile tool to study breast cancer-associated EMT and MET in vitro and in vivo.
| S-EPMC6092323 | biostudies-literature
Project description:Sporothrix schenckii 1099-18 Genome sequencing and assembly
| PRJNA218070 | ENA
Project description:An amendment to this paper has been published and can be accessed via a link at the top of the paper.
| S-EPMC7338367 | biostudies-literature