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

Cellular Signalling
Eunhye OhJae Hong Seo

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 3months. Our findings suggest a previously unknown role for USP34 in mammary gland development.

Citations

Feb 10, 2018·Cellular and Molecular Life Sciences : CMLS·Jihye Choi, Kwang-Hyun Baek
May 28, 2019·Journal of Biomedical Science·Ming-Jer YoungJan-Jong Hung
May 11, 2018·International Journal of Cancer. Journal International Du Cancer·Eunhye OhJi Young Kim
Nov 2, 2019·Essays in Biochemistry·Guillem LambiesVíctor M Díaz
Dec 27, 2018·Biochemical and Biophysical Research Communications·Hui WangYouming Xie
Oct 22, 2017·Biochimica Et Biophysica Acta. Reviews on Cancer·Saba HaqSuresh Ramakrishna
Oct 23, 2021·Biochemical Pharmacology·Mathilde MullardFranck Verrecchia

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