Dexamethasone resets stable association of nuclear Snail with LSD1 concomitant with transition from EMT to partial EMT

Satoshi Okuda, Nao Yamakado, Koichiro Higashikawa, Ryo Uetsuki, Fumi Ishida, Andra Rizqiawan, Shigehiro Ono, Kuniko Mizuta, Nobuyuki Kamata, Kei Tobiume

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1 Citation (Scopus)

Abstract

Cancer cells utilize epithelial to mesenchymal transition (EMT) during invasion and metastasis. This program has intermediate cell states with retained epithelial and gained mesenchymal features together, referred to as partial EMT. Histone demethylase LSD1 forms a complex with the EMT master transcription factor Snail to modify histone marks and regulate target gene expression. However, little is known about the formation of this complex during the Snail-dependent transition between partial EMT and EMT. Here we visualized the nuclear complex of Snail and LSD1 as foci signals using proximity ligation assay. We demonstrated that the nuclear foci numbers varied with the transition of exogenous Snail-dependent partial EMT to EMT. Furthermore, we found that long exposure to dexamethasone could revert exogenous Snail-dependent EMT to partial EMT. In this reversion, the nuclear foci numbers also returned to previous levels. Therefore, we concluded that Snail might select partial EMT or EMT by altering its association with LSD1.

Original languageEnglish
Article number101277
JournalBiochemistry and Biophysics Reports
Volume30
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Epithelial to mesenchymal transition (EMT)
  • LSD1
  • Partial EMT
  • Snail

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