PMID- 28499884 OWN - NLM STAT- MEDLINE DCOM- 20180306 LR - 20180828 IS - 1873-3913 (Electronic) IS - 0898-6568 (Linking) VI - 36 DP - 2017 Aug TI - Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial-mesenchymal transition and promotes stemness in mammary epithelial cells. PG - 230-239 LID - S0898-6568(17)30138-9 [pii] LID - 10.1016/j.cellsig.2017.05.009 [doi] AB - Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that regulates Axin stability and plays a critical role in Wnt/beta-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-beta-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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Oh, Eunhye AU - Oh E AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Kim, Ji Young AU - Kim JY AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Sung, Daeil AU - Sung D AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Cho, Youngkwan AU - Cho Y AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Lee, Nahyun AU - Lee N AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - An, Hyunsook AU - An H AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Kim, Yoon-Jae AU - Kim YJ AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Department of Biomedical Research Center, Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of Korea. FAU - Cho, Tae-Min AU - Cho TM AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. FAU - Seo, Jae Hong AU - Seo JH AD - Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea; Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. Electronic address: cancer@korea.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170510 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Transforming Growth Factor beta) RN - EC 3.4.19.12 (USP34 protein, human) RN - EC 3.4.19.12 (USP34 protein, mouse) RN - EC 3.4.19.12 (Ubiquitin-Specific Proteases) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cell Self Renewal/drug effects MH - Down-Regulation/drug effects MH - Epithelial Cells/drug effects/*metabolism MH - *Epithelial-Mesenchymal Transition/drug effects MH - Female MH - Gene Knockdown Techniques MH - Humans MH - Mammary Glands, Animal/*cytology MH - Mammary Glands, Human/*cytology MH - Mice MH - Neoplasm Invasiveness MH - RNA, Messenger/genetics/metabolism MH - Spheroids, Cellular/drug effects/metabolism MH - Stem Cells/drug effects/*metabolism MH - Transcription Factors/genetics/metabolism MH - Transforming Growth Factor beta/pharmacology MH - Ubiquitin-Specific Proteases/*antagonists & inhibitors/metabolism OTO - NOTNLM OT - EMT OT - Mammary gland development OT - Stemness OT - USP34 EDAT- 2017/05/14 06:00 MHDA- 2018/03/07 06:00 CRDT- 2017/05/14 06:00 PHST- 2017/01/09 00:00 [received] PHST- 2017/05/08 00:00 [revised] PHST- 2017/05/09 00:00 [accepted] PHST- 2017/05/14 06:00 [pubmed] PHST- 2018/03/07 06:00 [medline] PHST- 2017/05/14 06:00 [entrez] AID - S0898-6568(17)30138-9 [pii] AID - 10.1016/j.cellsig.2017.05.009 [doi] PST - ppublish SO - Cell Signal. 2017 Aug;36:230-239. doi: 10.1016/j.cellsig.2017.05.009. Epub 2017 May 10.