Dataset Information

Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

ABSTRACT: Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here, we show that in addition to inducing an epithelial mesenchymal transition, Snail promotes the cell-autonomous induction of Flk1(+) endothelial cells in an early subset of differentiating mouse embryonic stem (ES) cells. Cells that become Flk1+ in response to Snail have a transcriptional profile specific to Gata6+primitive endoderm, but not the early Nanog+epiblast. We further show that Snail's ability to promote Flk1(+) endothelium depends on fibroblast growth factor signaling as well as the repression of the microRNA-200 (miR-200) family, which directly targets the 3' UTRs of Flk1 and Ets1. Together, our results show that Snail is capable of inducing Flk1+ lineage commitment in a subset of differentiating ES cells through the down-regulation of the miR-200 family. We hypothesize that this mechanism of Snail-induced vasculogenesis may be conserved in both the early developing embryo and malignant cancers.

SUBMITTER: Gill JG

PROVIDER: S-EPMC3636466 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

Gill Jennifer G JG Langer Ellen M EM Lindsley R Coleman RC Cai Mi M Murphy Theresa L TL Murphy Kenneth M KM

Stem cells and development 20111018 2

Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here, we show that in addition to inducing an epithelial mesenchymal transition, Snail promotes the cell-autonomous ...[more]

PMID: 21861700

Similar Datasets

Project description:The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and metastasis in a variety of cancer types. In human breast cancer, gene expression studies have determined that basal-B/claudin-low and metaplastic cancers exhibit EMT-related characteristics, but the molecular mechanisms underlying this observation are unknown. As the family of miR-200 microRNAs has been shown to regulate EMT in normal tissues and cancer, here we evaluated whether the expression of the miR-200 family (miR-200f) and their epigenetic state correlate with EMT features in human breast carcinomas. We analyzed by qRT-PCR the expression of miR-200f members and various EMT-transcriptional inducers in a series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN), including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous (homologous or heterologous) differentiation. No MBCs with squamous differentiation were included. The DNA methylation status of miR-200f loci in tumor samples were inspected using Sequenom MassArray® MALDI-TOF platform. We also used two non-tumorigenic breast basal cell lines that spontaneously undergo EMT to study the modulation of miR-200f expression during EMT in vitro. We demonstrate that miR-200f is strongly decreased in MBCs compared with other cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f expression than ER+ tumors. Significantly, the decreased miR-200f expression found in MBCs is accompanied by an increase in the expression levels of EMT-transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar to tumor samples, we demonstrated that downregulation of miR-200f and hypermethylation of the miR-200c-141 locus, together with upregulation of EMT-transcriptional inducers also occur in an in vitro cellular model of spontaneous EMT. Thus, the expression and methylation status of miR-200f could be used as hypothetical biomarkers to assess the occurrence of EMT in breast cancer.

Dataset Information

Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

Publications

Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets