@article{be59a0d27dfd4fc286499052020179a5,
title = "Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features",
abstract = "Understanding the cell-of-origin of ovarian high grade serous cancer (HGSC) is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer. Recently, a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies. The cell-of-origin of this subtype of ovarian cancer is unknown. While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology, we unexpectedly found that the Yes-associated protein 1 (YAP1), the major effector of the Hippo signaling pathway, induced dedifferentiation and reprogramming of the ovarian granulosa cells, a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity, leading to the development of high grade ovarian cancer with serous features. Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.",
keywords = "Cell dedifferentiation, Cell reprogramming, Mesenchymal type of high grade serous cancer, Ovarian granulosa cells, The Hippo pathway, YAP1 oncogene",
author = "Xiangmin Lv and Chunbo He and Cong Huang and Guohua Hua and Xingcheng Chen and Timm, {Barbara K.} and Maclin, {Victoria M.} and Haggerty, {Abigail A.} and Aust, {Shelly K.} and Golden, {Denae M.} and Dave, {Bhavana J.} and Tseng, {Yun An} and Li Chen and Hongbo Wang and Peichao Chen and Klinkebiel, {David L.} and Karpf, {Adam R.} and Jixin Dong and Drapkin, {Ronny I.} and Rueda, {Bo R.} and Davis, {John S.} and Cheng Wang",
note = "Funding Information: This work was supported by the National Cancer Institute /the National Institute of Health ( 1R01CA197976 , 1R01CA201500 ), the Vincent Memorial Hospital Foundation /the Vincent Center for Reproductive Biology , the Olson Center for Women{\textquoteright}s Health ; University of Nebraska Medical Center Graduate Studies Fellowship; the Fred & Pamela Buffett Cancer Center (LB595); Colleen{\textquoteright}s Dream Foundation ; the Marsha Rivkin Center for Ovarian Cancer Research (the Barbara Learned Bridge Funding Award), and the CoBRE grant from the Nebraska Center for Cellular Signaling /the National Institute of General Medical Science /the National Institute of Health ( 5P30GM106397 ). We thank the Bioinformatics and Systems Biology Core at UNMC for providing genome-wide methylation profiling analysis services, which receives support from the Nebraska Research Initiative (NRI) and NIH ( 2P20GM103427 and 5P30CA036727 ). We thank Janice A. Taylor and James R. Talaska of the Advanced Microscopy Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy. We also thank Philip Hexley and Victoria B. Smith of The Flow Cytometry Research Facility at the University of Nebraska Medical Center for providing assistance with flow cytometry. Funding Information: This work was supported by the National Cancer Institute/the National Institute of Health (1R01CA197976, 1R01CA201500), the Vincent Memorial Hospital Foundation/the Vincent Center for Reproductive Biology, the Olson Center for Women's Health; University of Nebraska Medical Center Graduate Studies Fellowship; the Fred & Pamela Buffett Cancer Center (LB595); Colleen's Dream Foundation; the Marsha Rivkin Center for Ovarian Cancer Research (the Barbara Learned Bridge Funding Award), and the CoBRE grant from the Nebraska Center for Cellular Signaling/the National Institute of General Medical Science/the National Institute of Health (5P30GM106397). We thank the Bioinformatics and Systems Biology Core at UNMC for providing genome-wide methylation profiling analysis services, which receives support from the Nebraska Research Initiative (NRI) and NIH (2P20GM103427 and 5P30CA036727). We thank Janice A. Taylor and James R. Talaska of the Advanced Microscopy Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy. We also thank Philip Hexley and Victoria B. Smith of The Flow Cytometry Research Facility at the University of Nebraska Medical Center for providing assistance with flow cytometry. Xiangmin Lv and Chunbo He contributed to the experimental design, performance, data analysis, and manuscript preparation. Guohua Hua, Cong Huang, Xingcheng Chen, Jixin Dong, Li Chen, Hongbo Wang, and Peichao Chen assisted in completing in vivo experiments and data analysis. Barbara K. Timm and Victoria M. Maclin assisted in the preparation of primary cells. Abigail A. Haggerty, Shelly K. Aust, Denae M. Golden, and Bhavana J. Dave performed aCGH analysis. Adam R. Karpf and David L. Klinkebiel conducted the DNA methylation analysis. Yun-An Tseng and Ronny I. Drapkin assisted in the pathological analysis. John S. Davis contributed to the data analysis and manuscript preparation. Bo R. Rueda contributed to manuscript editing. Cheng Wang supervised these studies and contributed to the experimental design, data analysis, and manuscript preparation. Publisher Copyright: {\textcopyright} 2020 Science China Press",
year = "2020",
month = aug,
day = "15",
doi = "10.1016/j.scib.2020.03.040",
language = "English (US)",
volume = "65",
pages = "1281--1296",
journal = "Science Bulletin",
issn = "2095-9273",
publisher = "Springer Science + Business Media",
number = "15",
}