98%
921
2 minutes
20
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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654108 | PMC |
http://dx.doi.org/10.1016/j.scib.2020.03.040 | DOI Listing |
Bull Cancer
September 2025
Département d'oncologie médicale, centre Léon-Bérard (CLB-UNICANCER), université Claude-Bernard (UCB Lyon 1), Lyon, France. Electronic address:
Granulosa cell tumors (GCTs) are rare ovarian neoplasms, accounting for 2-5% of all ovarian cancers. Two histological types have been described: juvenile (JGCT) and adult (AGCT), the latter accounting for around 95% of the GCTs. AGCTs are mostly diagnosed at an early stage and commonly have a good prognosis.
View Article and Find Full Text PDFJ Cell Physiol
September 2025
Jiangxi Province Key Laboratory of Immunology and Inflammation, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Ovarian granulosa cells (GCs) are pivotal for follicular homeostasis, and their dysregulated apoptosis drives age-related ovarian aging. The Hippo signaling pathway, modulated by long noncoding RNAs (lncRNAs), is implicated in regulating GCs proliferation and ovarian aging. TEAD2 (Transcriptional Enhanced Associate Domain 2), a key downstream transcription factor of the Hippo signaling pathway, plays a critical role in regulating cell proliferation, apoptosis, and embryonic stem cell self-renewal.
View Article and Find Full Text PDFBiol Trace Elem Res
September 2025
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.
Ferroptosis is a form of iron-regulated cell death that plays a critical role in various aspects of female reproductive system development. These processes include the normal estrous cycle, ovarian formation, follicular maturation, ovulation, and pregnancy, all of which are essential for maintaining reproductive health in female animals. However, excessive iron leads to the accumulation of reactive oxygen species within cells, disrupting intracellular redox balance, inducing mitophagy, membrane rupture, and lipid peroxidation, which can damage tissues and cells, ultimately resulting in ferroptosis.
View Article and Find Full Text PDFJ Cell Mol Med
September 2025
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Diminished ovarian reserve (DOR) poses significant challenges in reproductive health, with emerging evidence implicating DNA damage repair pathways. While GADD45A is a critical regulator of DNA repair, cell cycle and apoptosis, its role in DOR pathogenesis remains unexplored. We employed transcriptome sequencing, qPCR and Western Blot analyses to compare GADD45A expression in granulosa cells (GCs) between DOR patients and controls.
View Article and Find Full Text PDFAnim Reprod Sci
September 2025
Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, Al. Mickiewicza 24/28, Krakow 30-059, Poland.
Irisin, a myokine/adipokine released during physical activity, has attracted attention for its regulatory effects on various physiological processes, including metabolism and reproduction. This study was performed to investigate the presence of fibronectin type III domain-containing protein 5 (FNDC5) in chicken granulosa cells (GCs) using immunocytochemistry and to assess the effect of irisin, the extracellular fragment of FNDC5, on these cells, which play a crucial role in progesterone (P4) production and follicle maturation. We measured cell viability, mRNA expression of the luteinising hormone receptor (LHR), the expression of steroidogenic genes (StAR, CYP11A1, and 3BHSD), and P4 secretion in GCs of chicken ovarian follicles.
View Article and Find Full Text PDF