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. Rueda; John S. Davis; Cheng Wang

doi:10.1016/j.scib.2020.03.040

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 journal › Article › peer-review

10 Scopus citations

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 language	English (US)
Pages (from-to)	1281-1296
Number of pages	16
Journal	Science Bulletin
Volume	65
Issue number	15
DOIs	https://doi.org/10.1016/j.scib.2020.03.040
State	Published - Aug 15 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

Access to Document

10.1016/j.scib.2020.03.040

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. (2020). 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

Lv, X, He, C, Huang, C, Hua, G, Chen, X, Timm, BK, Maclin, VM, Haggerty, AA, Aust, SK, Golden, DM, Dave, BJ, Tseng, YA, Chen, L, Wang, H, Chen, P, Klinkebiel, DL, Karpf, AR , Dong, J, Drapkin, RI, Rueda, BR, Davis, JS & Wang, C 2020, 'Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features', Science Bulletin, vol. 65, no. 15, pp. 1281-1296. https://doi.org/10.1016/j.scib.2020.03.040

@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 = "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 = "Elsevier B.V.",

number = "15",

}

TY - JOUR

T1 - Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features

AU - Lv, Xiangmin

AU - He, Chunbo

AU - Huang, Cong

AU - Hua, Guohua

AU - Chen, Xingcheng

AU - Timm, Barbara K.

AU - Maclin, Victoria M.

AU - Haggerty, Abigail A.

AU - Aust, Shelly K.

AU - Golden, Denae M.

AU - Dave, Bhavana J.

AU - Tseng, Yun An

AU - Chen, Li

AU - Wang, Hongbo

AU - Chen, Peichao

AU - Klinkebiel, David L.

AU - Karpf, Adam R.

AU - Dong, Jixin

AU - Drapkin, Ronny I.

AU - Rueda, Bo R.

AU - Davis, John S.

AU - Wang, Cheng

PY - 2020/8/15

Y1 - 2020/8/15

N2 - 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.

AB - 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.

KW - Cell dedifferentiation

KW - Cell reprogramming

KW - Mesenchymal type of high grade serous cancer

KW - Ovarian granulosa cells

KW - The Hippo pathway

KW - YAP1 oncogene

UR - http://www.scopus.com/inward/record.url?scp=85084209666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85084209666&partnerID=8YFLogxK

U2 - 10.1016/j.scib.2020.03.040

DO - 10.1016/j.scib.2020.03.040

M3 - Article

C2 - 34888112

AN - SCOPUS:85084209666

SN - 2095-9273

VL - 65

SP - 1281

EP - 1296

JO - Science Bulletin

JF - Science Bulletin

IS - 15

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this