Project description:Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-β, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-β and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-β-activated SMAD transcription factors in driving SNAIL expression and EMT program in mammary gland epithelial cells.
Project description:Epithelial-to-mesenchymal transitions (EMT) play prominent roles during development, regeneration and tumor progression. EMTs are triggered by TGF-β, RAS and other signals that cooperatively induce the expression of master EMT transcription factors such as SNAIL. Here, we elucidate how the TGF-β and RAS pathways jointly trigger EMTs and tie them to broader developmental programs. We identify RAS response element binding protein 1 (RREB1) as a critical partner of TGF-β-activated SMAD transcription factors in driving SNAIL expression in pancreatic pre-malignant epithelial cells, lung adenocarcinoma cells, and embryonic stem cells. Moreover, SMADs and RREB1 also drive EMT-associated fibrogenic programs in epithelial cells and mesendoderm differentiation in pluripotent embryonic cells. These findings illuminate the orchestration of EMT associated programs in gastrulation, fibrosis, and cancer.
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).
Project description:Recent studies demonstrate that Ca2+ signaling has an important role in EMT. Use of Ca2+ blockers such as 2APB can inhibit cell migration induced by TGF-β. Interestingly, we see an unexpected increase in Snail expression upon Ca2+ blocker treatment of both MCF10A and NMuMG cells; this increase is not observed with 2APB treatment alone. Therefore, we believe that 2APB plays a synergistic role with TGF-β in Snail induction. We propose to investigate the gene networks that change following 2APB +TGF-β treatment.
Project description:TGF-beta is one of the most important cytokines that induce epithelial to mesenchymal transition (EMT). In this dataset, we examined TGF-beta induced changes in gene and exon level expression. Core probesets of two samples were analyzed. NMuMG cells were stimulated with TGF-beta for 24 h or left untreated.
Project description:We report the gene expression in mouse NMuMG cells with or without UGCG depletion using RNA sequencing. After data analysis, the 11218 transcripts were identified. Among these transcripts, the TGF-β signaling target genes and EMT marker genes were significantly upregulated in UGCG depleted NMuMG cells. Then we used these genes and mouse TGF-β or EMT gene signatures to do the gene set enrichment analysis and showed the negative correlation of UGCG and TGF-β signaling or EMT in NMuMG cells.
Project description:Analysis of NMuMG cells expressing Osr2 or treated with TGF-ß. Results provide insight into a novel function of Osr2 in EMT induction.