@article{a5434df39f3c4b2c8997cabb04a54d92,
title = "USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation",
abstract = "The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential drug-gable target for this intractable disease.",
keywords = "Cancer stemness, Deubiquitinase, Pancreatic cancer, TCF7, USP21, Wnt pathway",
author = "Pingping Hou and Xingdi Ma and Qiang Zhang and Wu, {Chang Jiun} and Wenting Liao and Jun Li and Huamin Wang and Jun Zhao and Xin Zhou and Carolyn Guan and Jeffery Ackroyd and Shan Jiang and Jianhua Zhang and Spring, {Denise J.} and {Alan Wang}, Y. and DePinho, {Ronald A.}",
note = "Funding Information: We thank Zhaohui Xu and Ivonne Flores for mouse breeding, Howard Chang for technical assistance, and Haoqiang Ying, Guocan Wang, and Jian Hu for project discussions. P.H. is supported by the Seed Grant Program of the Hirshberg Foundation for Pancreatic Cancer Research. MD Anderson{\textquoteright}s Sequencing & Microarray Facility is supported by a Cancer Center Support Grant CA016672. This study is supported by National Institutes of Health R01 CA231349 grant (Y.A.W.) and National Cancer Institute P01 CA117969 grant (R.A.D.). C.G. was supported by the Cancer Prevention and Research Institute of Texas Research Training Program (RP170067). Funding Information: We thank Zhaohui Xu and Ivonne Flores for mouse breeding, Howard Chang for technical assistance, and Haoqiang Ying, Guocan Wang, and Jian Hu for project discussions. P.H. is supported by the Seed Grant Program of the Hirshberg Foundation for Pancreatic Cancer Research. MD Anderson's Sequencing & Microarray Facility is supported by a Cancer Center Support Grant CA016672. This study is supported by National Institutes of Health R01 CA231349 grant (Y.A.W.) and National Cancer Institute P01 CA117969 grant (R.A.D.). C.G. was supported by the Cancer Prevention and Research Institute of Texas Research Training Program (RP170067). Publisher Copyright: {\textcopyright} 2019 Hou et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.",
year = "2019",
month = oct,
day = "1",
doi = "10.1101/gad.326314.119",
language = "English (US)",
volume = "33",
pages = "1361--1366",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "19-20",
}