Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48230 | GEO | 2013/08/01
SECONDARY ACCESSION(S): PRJNA209306
REPOSITORIES: GEO
Similar Datasets
Project description:This paper shows, for the first time, a novel function of the OVO-like proteins (OVOL1and OVOL2) as critical inducers of mesenchymal to epithelial transition (MET) in human cancer. Examination of the effects of OVOL1 and OVOL2 overexpression in a prostate cancer model.
2013-08-01 | E-GEOD-48230 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3790720 | biostudies-literature
Project description:Mesenchymal-to-epithelial transition (MET) is an important step in cell reprogramming from fibroblast, a most frequently used cell type for this purpose, to various epithelial cell types. However, how MET can be induced in fibroblast has not been fully studied. In this study, we sought for transcription factors (TFs) that can efficiently induce MET in dermal fibroblasts and identified OVOL2 as a potent inducer of key epithelial genes. In addition, OVOL2 cooperatively enhanced MET induced by HNF1A, TP63 and KLF4, known reprogramming TFs to epithelial lineages. In TP63/KLF4-induced fibroblast-keratinocyte cell reprogramming, OVOL2 greatly facilitated activation of epithelial genes as well as keratinocyte-specific genes. This enhancement of epithelial gene expression program was accompanied by enhanced changes in chromatin accessibility across the genome. Mechanistically, motif enrichment analysis revealed that target loci of KLF4 and TP63 become accessible upon reprogramming while OVOL2 target loci become inaccessible, indicating that KLF4 and TP63 positively regulate their targets while OVOL2 primarily induces closed chromatin state at its target loci. Thus, OVOL2 and tissue-specific reprogramming factors cooperatively facilitate cell reprogramming of fibroblast into epithelial lineages through distinct mechanisms.
2019-05-17 | GSE122034 | GEO
Project description:Mesenchymal-to-epithelial transition (MET) is an important step in cell reprogramming from fibroblast, a most frequently used cell type for this purpose, to various epithelial cell types. However, how MET can be induced in fibroblast has not been fully studied. In this study, we sought for transcription factors (TFs) that can efficiently induce MET in dermal fibroblasts and identified OVOL2 as a potent inducer of key epithelial genes. In addition, OVOL2 cooperatively enhanced MET induced by HNF1A, TP63 and KLF4, known reprogramming TFs to epithelial lineages. In TP63/KLF4-induced fibroblast-keratinocyte cell reprogramming, OVOL2 greatly facilitated activation of epithelial genes as well as keratinocyte-specific genes. This enhancement of epithelial gene expression program was accompanied by enhanced changes in chromatin accessibility across the genome. Mechanistically, motif enrichment analysis revealed that target loci of KLF4 and TP63 become accessible upon reprogramming while OVOL2 target loci become inaccessible, indicating that KLF4 and TP63 positively regulate their targets while OVOL2 primarily induces closed chromatin state at its target loci. Thus, OVOL2 and tissue-specific reprogramming factors cooperatively facilitate cell reprogramming of fibroblast into epithelial lineages through distinct mechanisms.
2019-05-17 | GSE122035 | GEO
Project description:Multiple EMT-promoting/inhibiting transcription factors have been identified including Snail, Zeb1 and Ovol2. To understand differential roles of these factors, we performed gene expression profiling by RNA-seq upon Snail-/Zeb1-induced EMT or Ovol2-induced MET in human mammary epithelial MCF10A cells.
2019-07-01 | GSE70551 | GEO
Project description:Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). Recent studies suggest that EMT endows differentiated epithelial cells with stem cell traits, posing the interesting question of how epithelial plasticity is properly restricted to ensure epithelial differentiation during tissue morphogenesis. Here we identify zinc-finger transcription factor Ovol2 as a key suppressor of EMT of mammary epithelial cells. Epithelia-specific deletion of Ovol2 completely arrests mammary ductal morphogenesis, and depletes epithelial stem/progenitor cell reservoirs. Further, Ovol2-deficient epithelial cells undergo EMT in vivo to become non-epithelial cell types, and that Ovol2 directly represses key EMT inducers such as Zeb1 and regulates stem/progenitor cell responsiveness to TGF-beta. We also provide evidence for a suppressive role of Ovol2 in breast cancer progression. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity to balance stemness with epithelial differentiation in development and cancer. We report ChIPseq data illustrating Ovol2 genome-wide targets in mouse mammary epithelial cells, suggesting that Ovol2 regulates a plethora of genes associated with the EMT process. Immunoprecipitated samples from HC11 mouse mammary epithelial cells with antibodies against Ovol2 and control IgG respectively were used for ChIP-seq experiments.
2014-03-19 | E-GEOD-53925 | biostudies-arrayexpress
Project description:Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). Recent studies suggest that EMT endows differentiated epithelial cells with stem cell traits, posing the interesting question of how epithelial plasticity is properly restricted to ensure epithelial differentiation during tissue morphogenesis. Here we identify zinc-finger transcription factor Ovol2 as a key suppressor of EMT of mammary epithelial cells. Epithelia-specific deletion of Ovol2 completely arrests mammary ductal morphogenesis, and depletes epithelial stem/progenitor cell reservoirs. Further, Ovol2-deficient epithelial cells undergo EMT in vivo to become non-epithelial cell types, and that Ovol2 directly represses key EMT inducers such as Zeb1 and regulates stem/progenitor cell responsiveness to TGF-beta. We also provide evidence for a suppressive role of Ovol2 in breast cancer progression. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity to balance stemness with epithelial differentiation in development and cancer. We report ChIPseq data illustrating Ovol2 genome-wide targets in mouse mammary epithelial cells, suggesting that Ovol2 regulates a plethora of genes associated with the EMT process.
2014-03-19 | GSE53925 | GEO
Project description:Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). Recent studies suggest that EMT endows differentiated epithelial cells with stem cell traits, posing the interesting question of how epithelial plasticity is properly restricted to ensure epithelial differentiation during tissue morphogenesis. Here we identify zinc-finger transcription factor Ovol2 as a key suppressor of EMT of mammary epithelial cells. Epithelia-specific deletion of Ovol2 completely arrests mammary ductal morphogenesis, and depletes epithelial stem/progenitor cell reservoirs. Further, Ovol2-deficient epithelial cells undergo EMT in vivo to become non-epithelial cell types, and that Ovol2 directly represses key EMT inducers such as Zeb1 and regulates stem/progenitor cell responsiveness to TGF-beta. We also provide evidence for a suppressive role of Ovol2 in breast cancer progression. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity to balance stemness with epithelial differentiation in development and cancer. TEBs from control and conditional Ovol2-knockout mammary glands were physically isolated for RNA extraction and hybridization on Affymetrix microarrays. In order to identify primary changes, we analyzed TEBs from 24-25-day-old mice, when morphological differences between control and Ovol2 SSKO were still minimal.
2014-03-19 | E-GEOD-53923 | biostudies-arrayexpress
Project description:Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). However, it is still unknown whether and how epithelial plasticity is kept in check in epithelial cells during development. Here we show that restricting the EMT of mammary epithelial cells by transcription factor Ovol2 is required for proper morphogenesis and regeneration. Deletion of Ovol2 blocks mammary ductal morphogenesis, depletes stem/progenitor cell reservoirs, and leads epithelial cells to undergo EMT in vivo to become non-epithelial cell types. Ovol2 directly represses myriad EMT inducers and its absence switches response to TGF-beta from growth arrest to EMT. Furthermore, forced expression of the repressor isoform of Ovol2 is able to reprogram metastatic breast cancer cells from a mesenchymal to an epithelial state. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity in development and cancer. Refer to individual Series
2014-03-19 | E-GEOD-54126 | biostudies-arrayexpress
Project description:Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition or EMT). Recent studies suggest that EMT endows differentiated epithelial cells with stem cell traits, posing the interesting question of how epithelial plasticity is properly restricted to ensure epithelial differentiation during tissue morphogenesis. Here we identify zinc-finger transcription factor Ovol2 as a key suppressor of EMT of mammary epithelial cells. Epithelia-specific deletion of Ovol2 completely arrests mammary ductal morphogenesis, and depletes epithelial stem/progenitor cell reservoirs. Further, Ovol2-deficient epithelial cells undergo EMT in vivo to become non-epithelial cell types, and that Ovol2 directly represses key EMT inducers such as Zeb1 and regulates stem/progenitor cell responsiveness to TGF-beta. We also provide evidence for a suppressive role of Ovol2 in breast cancer progression. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity to balance stemness with epithelial differentiation in development and cancer.
2014-03-19 | GSE53923 | GEO