Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features

Xiangmin Lv, Chunbo He, Cong Huang, Guohua Hua, Xingcheng Chen, Barbara K. Timm, Victoria M. Maclin, Abigail A. Haggerty, Shelly K. Aust, Denae M. Golden, Bhavana J. Dave, Yun An Tseng, Li Chen, Hongbo Wang, Peichao Chen, David L. Klinkebiel, Adam R. Karpf, Jixin Dong, Ronny I. Drapkin, Bo R. RuedaJohn S. Davis, Cheng Wang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1281-1296
Number of pages16
JournalScience Bulletin
Volume65
Issue number15
DOIs
StateAccepted/In press - 2020

Keywords

  • Cell dedifferentiation
  • Cell reprogramming
  • Mesenchymal type of high grade serous cancer
  • Ovarian granulosa cells
  • The Hippo pathway
  • YAP1 oncogene

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features'. Together they form a unique fingerprint.

  • Cite this

    Lv, X., He, C., Huang, C., Hua, G., Chen, X., Timm, B. K., Maclin, V. M., Haggerty, A. A., Aust, S. K., Golden, D. M., Dave, B. J., Tseng, Y. A., Chen, L., Wang, H., Chen, P., Klinkebiel, D. L., Karpf, A. R., Dong, J., Drapkin, R. I., ... Wang, C. (Accepted/In press). Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features. Science Bulletin, 65(15), 1281-1296. https://doi.org/10.1016/j.scib.2020.03.040