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PLoS Genet. 2018 Nov 30;14(11):e1007826. doi: 10.1371/journal.pgen.1007826. eCollection 2018 Nov.

Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition.

Author information

1
Division of Molecular and Vascular Biology, IRDA, Kumamoto University, Kumamoto, Japan.
2
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
3
Division of Disease Epigenetics, IRDA, Kumamoto University, Kumamoto, Japan.
4
Division of Genome Sciences, RCAST, The University of Tokyo, Tokyo, Japan.
5
Division of Metabolic Medicine, RCAST, The University of Tokyo, Tokyo, Japan.
6
Isotope Science Center, The University of Tokyo, Tokyo, Japan.

Abstract

Endothelial cell (EC) plasticity in pathological settings has recently been recognized as a driver of disease progression. Endothelial-to-mesenchymal transition (EndMT), in which ECs acquire mesenchymal properties, has been described for a wide range of pathologies, including cancer. However, the mechanism regulating EndMT in the tumor microenvironment and the contribution of EndMT in tumor progression are not fully understood. Here, we found that combined knockdown of two ETS family transcription factors, ERG and FLI1, induces EndMT coupled with dynamic epigenetic changes in ECs. Genome-wide analyses revealed that ERG and FLI1 are critical transcriptional activators for EC-specific genes, among which microRNA-126 partially contributes to blocking the induction of EndMT. Moreover, we demonstrated that ERG and FLI1 expression is downregulated in ECs within tumors by soluble factors enriched in the tumor microenvironment. These data provide new insight into the mechanism of EndMT, functions of ERG and FLI1 in ECs, and EC behavior in pathological conditions.

PMID:
30500808
PMCID:
PMC6291168
DOI:
10.1371/journal.pgen.1007826
[Indexed for MEDLINE]
Free PMC Article

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