Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial-mesenchymal transition and promotes stemness in mammary epithelial cells

Eunhye Oh, Ji Young Kim, Daeil Sung, Youngkwan Cho, Nahyun Lee, Hyunsook An, Yoon Jae Kim, Tae Min Cho, Jae Hong Seo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that regulates Axin stability and plays a critical role in Wnt/β-catenin signaling. We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT) induction and its effects on mammary epithelial stem cells. USP34 expression levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced EMT, as evidenced by the upregulation of EMT markers including N-cadherin, phospho-Smad3, Snail and active-β-catenin, as well as the downregulation of Axin 1 and E-cadherin. USP34 knockdown (KD) in these cells also resulted in the acquisition of invasive behavior, and promoted stemness as indicated by enhanced mammosphere-forming ability, concomitant with the upregulation of Nanog, Oct4 and Sox2 mRNA expression. Endogenous USP34 expression was observed to be at low levels in virgin mouse mammary glands in vivo. When USP34-KD cells were transplanted into the cleared mammary fat pads (CFP) of mice, these cells reconstituted the mammary gland with ductal tree development within 3 months. Our findings suggest a previously unknown role for USP34 in mammary gland development.

Original languageEnglish
Pages (from-to)230-239
Number of pages10
JournalCellular Signalling
Volume36
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

  • EMT
  • Mammary gland development
  • Stemness
  • USP34

ASJC Scopus subject areas

  • Cell Biology

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