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

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	Accepted/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

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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

Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features. / Lv, Xiangmin; He, Chunbo; Huang, Cong; Hua, Guohua; Chen, Xingcheng; Timm, Barbara K.; Maclin, Victoria M.; Haggerty, Abigail A.; Aust, Shelly K.; Golden, Denae M.; Dave, Bhavana J.; Tseng, Yun An; Chen, Li; Wang, Hongbo; Chen, Peichao; Klinkebiel, David L.; Karpf, Adam R.; Dong, Jixin; Drapkin, Ronny I.; Rueda, Bo R.; Davis, John S.; Wang, Cheng.

In: Science Bulletin, Vol. 65, No. 15, 15.08.2020, p. 1281-1296.

Research output: Contribution to journal › Article

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

Lv, Xiangmin ; He, Chunbo ; Huang, Cong ; Hua, Guohua ; Chen, Xingcheng ; Timm, Barbara K. ; Maclin, Victoria M. ; Haggerty, Abigail A. ; Aust, Shelly K. ; Golden, Denae M. ; Dave, Bhavana J. ; Tseng, Yun An ; Chen, Li ; Wang, Hongbo ; Chen, Peichao ; Klinkebiel, David L. ; Karpf, Adam R. ; Dong, Jixin ; Drapkin, Ronny I. ; Rueda, Bo R. ; Davis, John S. ; Wang, Cheng. / Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features. In: Science Bulletin. 2020 ; Vol. 65, No. 15. pp. 1281-1296.

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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.",

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AU - Chen, Xingcheng

AU - Timm, Barbara K.

AU - Maclin, Victoria M.

AU - Haggerty, Abigail A.

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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

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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.

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