Analysis of gene expression changes during long-term induction of EMT in EpRas tumor cells by TGF-b1.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59922 | GEO | 2014/09/01
SECONDARY ACCESSION(S): PRJNA257067
REPOSITORIES: GEO
Similar Datasets
Project description:EMT is a developmental process, which can be reactivated in cancer cells. Cancer cells maintaining EMT in the circulation may have pro-metastatic properties. We used microarrays to profile EMT-related gene expression changes after 14 d of TGF-b1 treatment. EpRas cells were cultured in standard conditions either in the presence of absence of recombinant TGF-b1 (2 ng/ml) for 14 d. After this period, RNA was isolated from triplicate wells of treated and non-treated cells, and hybridized on Affymetrix microarrays.
2014-09-01 | E-GEOD-59922 | biostudies-arrayexpress
Project description:The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor β1 (TGF-b1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGF-b1 stimulated breast cancer cells with EMT properties migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and receptors that could be involved in this. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL-7/IL7R and IL-15/IL15R as pairs of chemokines and chemokine receptors with potential roles in promoting chemotactic migration of breast cancer cells with EMT properties towards the lymphatics. The results warrant studies to further explore their possible roles in lymph metastasis in breast cancer. Moreover, they demonstrate the capacity of TGF-b1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells.
2023-12-13 | GSE241881 | GEO
Project description:Response of mouse mammary epithelial cells NMuMG to TGF-b1 - time course experiment. Identification of novel gene targets involved in TGF-b1-driven regulation of epithelial-mesenchymal transition (EMT).
2004-10-01 | E-MEXP-139 | biostudies-arrayexpress
Project description:Background: Epithelial-to-mesenchymal transition (EMT) is considered an important driving mechanism behind aggressive cancer phenotype. This was recently challenged by the finding that cells can metastasize without undergoing EMT. However, the same studies confirmed the important role of the EMT program in drug resistance. The EMT program is largely dependent on the cell’s microenvironment. Acriflavine (ACF) is a heteroaromatic dye with antibacterial and antiviral effects. Recently, ACF was suggested as anticancer agent for its topoisomerase inhibitor activity. ACF further blocks the hypoxia-inducible factor (HIF) pathway, an important driver of cancer aggressiveness. How ACF works in cancer is however unknown. Aim: Identification of the working mechanism, molecular pathways and signaling of ACF in EMT cancer cells. To this end, three in vitro models were developed of EMT induction (human pancreatic cancer cells stimulated with TGF-b1, human pancreatic cancer cells stimulated with CoCl2, drug resistance against sorafenib in human liver cancer cells). Only the first model - PANC1 stimulated with TGF-b1 - is discussed in this GEO submission.
2017-03-08 | GSE82293 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is a key cellular process involved in development and disease progression. Single-cell transcriptomes can reveal intermediate EMT states observed in tumors, but previous studies focused on time-dependent responses in epithelial cells after stimulation with EMT signals as an in vitro model for understanding EMT progression, so it was unclear how transcriptomes can change in response to different levels of EMT inducer. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with various concentrations of TGF-β. We found that the dose-dependent EMT harbors multiple intermediate states at the single-cell level after two weeks of treatment, suggesting a stable EMT continuum. After correcting batch effects from experiments, we performed comparative analyses of the dose- and time-dependent EMT. We found that the dose-dependent EMT shows a stronger anti-correlation between epithelial and mesenchymal transcriptional programs and a better resolution of stages of EMT compared to the time-dependent progress. These properties enable more power to detect genes whose expressions are associated with EMT. Nonetheless, our analyses showed cell clusters unique to the time-dependent EMT, which correspond to en route cell populations that do not appear at steady states. Furthermore, combining dose- and time-dependent cell clusters gave rise to more accurate prognosis for cancer patients compared to individual EMT spectrum.
2022-08-29 | GSE200941 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is a key cellular process involved in development and disease progression. Single-cell transcriptomes can reveal intermediate EMT states observed in tumors, but previous studies focused on time-dependent responses in epithelial cells after stimulation with EMT signals as an in vitro model for understanding EMT progression, so it was unclear how transcriptomes can change in response to different levels of EMT inducer. Here, we performed single-cell RNA-sequencing with human mammary epithelial cells treated with various concentrations of TGF-β. We found that the dose-dependent EMT harbors multiple intermediate states at the single-cell level after two weeks of treatment, suggesting a stable EMT continuum. After correcting batch effects from experiments, we performed comparative analyses of the dose- and time-dependent EMT. We found that the dose-dependent EMT shows a stronger anti-correlation between epithelial and mesenchymal transcriptional programs and a better resolution of stages of EMT compared to the time-dependent progress. These properties enable more power to detect genes whose expressions are associated with EMT. Nonetheless, our analyses showed cell clusters unique to the time-dependent EMT, which correspond to en route cell populations that do not appear at steady states. Furthermore, combining dose- and time-dependent cell clusters gave rise to more accurate prognosis for cancer patients compared to individual EMT spectrum.
2022-09-20 | GSE213753 | GEO
Project description:Long-term peritoneal dialysis is associated with progressive fibrosis of the peritoneum. Epithelial-mesenchymal transition (EMT) of mesothelial cells is an important mechanism involved in peritoneal fibrosis, and TGF-b1 is considered central in this process. We conducted network-based integrated analysis of transcriptomic data to systemically characterize the molecular signature of TGF-b1-stimulated human peritoneal mesothelial cells (HPMCs).
2018-10-18 | GSE121372 | GEO
Project description:Transforming growth factor- (TGF-) signaling is a critical driver of epithelial–mesenchymal transition (EMT) and cancer progression. However, the regulatory roles of long non-coding RNAs (lncRNAs) in TGF--induced EMT and cancer progression are not well understood. Here, we identified an unannotated nuclear lncRNA LETS1 (LncRNA Enforcing TGF- Signaling 1) as a novel TGF-/SMAD target gene. Loss of LETS1 attenuates TGF--induced EMT, migration and extravasation in breast and lung cancer cells. LETS1 potentiates TGF-/SMAD signaling by stabilizing cell surface TGF- type I receptor (TRI) and thereby forms a positive feedback loop. Mechanistically, LETS1 inhibits TRI polyubiquitination by inducing the orphan nuclear receptor 4A1 (NR4A1) expression, a critical determinant of a destruction complex for inhibitory SMAD7. An unbiased interactome analysis identified the Nuclear Factor of Activated T Cells (NFAT5) as a protein partner of LETS1 to mediate activation of NR4A1 promoter. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA and elucidate the mechanism by which nuclear LETS1 potentiates TGF- receptor signaling.
2023-07-31 | PXD037401 | Pride
Project description:Lamins (A/C and B) are type V intermediate filaments and constitute the major cytoskeleton component of nuclei. They are assembled forming a filamentous meshwork that is mainly located between the inner nuclear membrane and the peripheral chromatin in where they form structural and conserved elements called lamin-associated domains (LADs) that cover around 40% of the mammalian genome. However, a small fraction of lamins are also located in the nucleoplasm although is still unclear if represents a fraction that is in transit towards the nuclear membrane, a reservoir for protein turnover or they have specific functions in nuclear organization6. Here we mapped genome-wide the localization of lamin B1 from an enriched euchromatin fraction. Our analysis show for the first time that lamin B1 can be also associated with active euchromatin forming domains of about half a megabase on average in size. These euchromatin lamin B1 domains (eLADs) are constituted by active and accessible euchromatin showed by RNAseq and ATACseq. Importantly, we have analyzed its behavior at the onset of the epithelial to mesenchymal transition (EMT), a cellular transformation process essential during development and reactivated in cancer cells. Our results suggest that eLADs are dynamic and functional during EMT. Finally, Hi-C data during this cellular transformation showed changes in the frequency of chromatin contacts around the TSS in genes enriched in lamin B1 before the generation of new regulatory elements in the mesenchymal state. Taken together, these results demonstrate that not only heterochromatin but euchromatin is organized into lamin domains as well. Moreover, these eLADs are dynamic, functional and essential for chromatin organization and gene regulation during the EMT.
2018-08-30 | GSE96033 | GEO
Project description:Regulation of organismal homeostasis in response to nutrient availability is a vital physiological process that involves inter-organ communication. Understanding the mechanisms controlling systemic cross talk for maintenance of metabolic health is critical to counteract diet-induced obesity. Here, we show that cardiac-derived transforming growth factor beta 1 (TGF-b1) protects against weight gain and glucose intolerance in mice subjected to high-fat diet. Secretion of TGF-b1 by cardiomyocytes correlates with bioavailability of this factor in circulation. TGF-b1 prevents adipose tissue inflammation independent of body weight and glucose metabolism phenotypes, suggesting protection from adipocyte dysfunction-driven immune cell recruitment. TGF-b1 alters gene expression programs in white adipocytes, favoring their thermogenic fate and consequently increasing their mitochondrial oxygen consumption rates. Ultimately, subcutaneous and visceral white adipose tissue from heart-specific TGF-b1 transgenic mice fail to undergo cellular hypertrophy, leading to reduced overall adiposity during high-fat feeding. Thus, TGF-b1 is a critical mediator of heart-fat communication for regulation of systemic metabolism.
2021-11-03 | GSE179102 | GEO