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.

了解卵巢高级浆液性癌（HGSC）的细胞起源是有效预防和早期诊断这种最致命的妇科癌症的先决条件。最近，TCGA 和 AOCS 研究均发现卵巢癌中预后最差的间质型卵巢 HGSC。这种卵巢癌亚型的细胞起源尚不清楚。在研究Hippo信号通路在卵巢颗粒细胞生理学和病理学中的作用时，我们意外地发现，Hippo信号通路的主要效应子Yes相关蛋白1（YAP1）诱导卵巢颗粒细胞的去分化和重编程。细胞是一种独特类型的卵巢滤泡细胞，具有间充质谱系和高可塑性，导致具有浆液性特征的高级卵巢癌的发展。我们的研究结果揭示了具有间充质特征的 HGSC 亚型的潜在细胞起源。