@article{b452df749e004dfea365f82e2ca71ec2,
title = "Loss of ZIP facilitates JAK2-STAT3 activation in tamoxifen-resistant breast cancer",
abstract = "Tamoxifen, a widely used modulator of the estrogen receptor (ER), targets ER-positive breast cancer preferentially. We used a powerful validation-based insertion mutagenesis method to find that expression of a dominant-negative, truncated form of the histone deacetylase ZIP led to resistance to tamoxifen. Consistently, increased expression of full-length ZIP gives the opposite phenotype, inhibiting the expression of genes whose products mediate resistance. An important example is JAK2. By binding to two specific sequences in the promoter, ZIP suppresses JAK2 expression. Increased expression and activation of JAK2 when ZIP is inhibited lead to increased STAT3 phosphorylation and increased resistance to tamoxifen, both in cell culture experiments and in a mouse xenograft model. Furthermore, data from human tumors are consistent with the conclusion that decreased expression of ZIP leads to resistance to tamoxifen in ERpositive breast cancer.",
keywords = "JAK/STAT, VBIM, ZIP, tamoxifen resistance",
author = "Ning Zhu and Jing Zhang and Yuping Du and Xiaodong Qin and Ruidong Miao and Jing Nan and Xing Chen and Jingjie Sun and Rui Zhao and Xinxin Zhang and Lei Shi and Xin Li and Yuxi Lin and Wei Wei and Aihong Mao and Zhao Zhang and Stark, {George R.} and Yuxin Wang and Jinbo Yang",
note = "Funding Information: ACKNOWLEDGMENTS. This work was funded by NIH Grant PO1 CA062220 (to G.R.S.) and by Major Science and Technology Innovation Project for Marine Drugs of Shandong Province Grant 2018SDKJ0402-3, National Science and Technology Major Project for Significant New Drugs Development Grant 2018ZX09735-004, and National Natural Science Foundation of China Grant 31571439 (to J.Y.). We thank Dr. Yongfeng Shang and Dr. Sapin Constantinescu for generously sharing plasmids and Dr. Xuan Liu for helpful technical support and discussions. We thank Hongyun Guo for assistance with patient samples from The Bank of Patient Specimens, Gansu Provincial Cancer Hospital, Gansu Provincial Academic Institute for Medical Research. Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = jun,
day = "30",
doi = "10.1073/pnas.1910278117",
language = "English (US)",
volume = "117",
pages = "15047--15054",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "26",
}