Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial-mesenchymal transition and promotes stemness in mammary epithelial cells
| Autor: | Daeil Sung, Yoon Jae Kim, Ji Young Kim, Hyunsook An, Nahyun Lee, Eunhye Oh, Tae Min Cho, Youngkwan Cho, Jae Hong Seo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Homeobox protein NANOG Epithelial-Mesenchymal Transition Mammary gland Down-Regulation Biology Mice 03 medical and health sciences Mammary Glands Animal 0302 clinical medicine SOX2 Downregulation and upregulation Transforming Growth Factor beta Cell Line Tumor Spheroids Cellular medicine Animals Humans Neoplasm Invasiveness RNA Messenger Epithelial–mesenchymal transition Cell Self Renewal Mammary Glands Human Gene knockdown Stem Cells Wnt signaling pathway Epithelial Cells Cell Biology 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research Female Ubiquitin-Specific Proteases Stem cell Transcription Factors |
| Zdroj: | Cellular Signalling. 36:230-239 |
| ISSN: | 0898-6568 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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