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

Nao Nagai, Hiroto Ohguchi, Ryo Nakaki, Yoshihiro Matsumura, Yasuharu Kanki, Juro Sakai, Hiroyuki Aburatani, Takashi Minami

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Article numbere1007826
JournalPLoS Genetics
Volume14
Issue number11
DOIs
Publication statusPublished - 2018 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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