C-terminal domain small phosphatase-like 2 promotes epithelial-to-mesenchymal transition via Snail dephosphorylation and stabilization

Open Biol. 2018 Apr;8(4):170274. doi: 10.1098/rsob.170274.

Abstract

The epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process converting epithelial cells into mesenchymal cell morphology. Snail is a critical regulator of EMT by both suppressing epithelial gene expression and promoting mesenchymal gene expression. Expression and activity of Snail are tightly controlled at transcriptional and post-translational levels. It has previously been reported that Snail undergoes phosphorylation and ubiquitin-dependent proteasome degradation. Here, we report nuclear phosphatase SCP4/CTDSPL2 acts as a novel Snail phosphatase. SCP4 physically interacts with and directly dephosphorylates Snail. SCP4-mediated dephosphorylation of Snail suppresses the ubiquitin-dependent proteasome degradation of Snail and consequently enhances TGFβ-induced EMT. The knockdown of SCP4 in MCF10A mammary epithelial cells leads to attenuated cell migration. Collectively, our finding demonstrates that SCP4 plays a critical role in EMT through Snail dephosphorylation and stabilization.

Keywords: CTDSPL2/SCP4; EMT; Snail; TGF-β signalling; phosphatase; phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoprotein Phosphatases / physiology*
  • Phosphorylation
  • Snail Family Transcription Factors / metabolism*
  • Snail Family Transcription Factors / physiology

Substances

  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • CTDSPL2 protein, human
  • Phosphoprotein Phosphatases