Reprogramming of Ovarian Granulosa Cells by YAP1 Leads to Development of High-Grade Cancer with Mesenchymal Lineage and Serous Features

Overview

Journal Sci Bull (Beijing)

Specialty Science

Date 2021 Dec 10

PMID 34888112

Citations 8

Authors

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

Affiliations

Soon will be listed here.

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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