Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development DOI Creative Commons
Robbin Nameki, Heidi Chang, Pak Yu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 12, 2023

ABSTRACT The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous ‘ovarian’ cancer (HGSC), yet their cooperative role in the hypothesized tissue origin, fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq HiC) data sets 24 profiles RNA-seq factor knock-down followed by RNA sequencing FTSEC HGSC models to define binding sites gene regulated these cis trans . This revealed that lineage-enriched, super-enhancer associated whose DNA-binding patterns target genes re-wired during tumor development. All four TFs were indispensable for clonogenicity survival but only depletion PAX8 impaired cell survival. These pharmacologically inhibited transcriptional inhibitors HGSCs not FTSECs. Collectively, our highlights tumor-specific epigenetic remodeling tightly related activity targetable a manner through inhibitors.

Language: Английский

Single-cell transcriptomic analysis of endometriosis DOI
Marcos A. Fonseca,

Marcela Haro,

Kelly N. Wright

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 255 - 267

Published: Jan. 9, 2023

Language: Английский

Citations

89
Biology-driven therapy advances in high-grade serous ovarian cancer DOI Creative Commons
Yinu Wang, Alexander James Duval, Mazhar Adli

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(1)

Published: Jan. 1, 2024

Following a period of slow progress, the completion genome sequencing and paradigm shift relative to cell origin for high grade serous ovarian cancer (HGSOC) led new perspective on biology therapeutic solutions this deadly cancer. Experimental models were revisited address old questions, improved tools generated. Additional pathways emerging as drivers tumorigenesis key dependencies targeting, in particular, VEGF-driven angiogenesis homologous recombination deficiency, discovered. Molecular profiling histological subtypes defined distinct genetic events each entity, enabling first attempts toward personalized treatment. Armed with knowledge, HGSOC treatment was revised include agents. Among them, PARP inhibitors (PARPis) shown induce unprecedented improvement clinical benefit selected subsets patients. Research mechanisms resistance PARPis is beginning discover vulnerabilities point possibilities. This Review highlights these advances, remaining challenges, unsolved problems field.

Language: Английский

Citations

21
A cutting-edge investigation of the multifaceted role of SOX family genes in cancer pathogenesis through the modulation of various signaling pathways DOI
Saade Abdalkareem Jasim,

Shireen Hamid Farhan,

Irfan Ahmad

et al.

Functional & Integrative Genomics, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 4, 2025

Language: Английский

Citations

1
SOX17: A Highly Sensitive and Specific Immunomarker for Ovarian and Endometrial Carcinomas DOI Creative Commons
Xudong Zhang, Jun Yao, Na Niu

et al.

Modern Pathology, Journal Year: 2023, Volume and Issue: 36(2), P. 100001 - 100001

Published: Jan. 9, 2023

PAX8 is the most commonly used immunomarker to link a carcinoma gynecologic tract; however, it lacks specificity. Through mining The Cancer Genome Atlas mRNA expression profile data, we identified SOX17 as potential specific marker at level for tumors. To evaluate utility of this in identification origin given carcinoma, performed immunochemical staining large cohort ovarian and endometrial cancer cases (n = 416), together with solid tumors from other organs 1544) tissue microarrays. Similar PAX8, was highly expressed different subtypes (97.5% vs 97% serous 90% endometrioid 100% clear cell carcinoma), except mucinous (0% 27%), also (88% 84% carcinoma). not thyroid renal carcinomas, whereas high (86% 85%, respectively). In addition, low levels cervical adenocarcinoma (20%) had no squamous mesothelioma, carcinomas breast, lung, pancreas, colon, stomach, liver, bladder, salivary gland. Our data indicate that only sensitive but carcinomas.

Language: Английский

Citations

17
SOX on tumors, a comfort or a constraint? DOI Creative Commons

Junqing Jiang,

Yufei Wang, Mengyu Sun

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 9, 2024

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation SOX members closely associated tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research investigate mechanisms functions confusion remains regarding aspects such as immune microenvironment (TIME) contradictory impacts exerts on tumors. This review summarizes physiological function multiple roles tumors, focus relationship between TIME, aiming propose potential cancer promising methods for treatment.

Language: Английский

Citations

7
Targeting NaPi2b in ovarian cancer DOI
Susana Banerjee, Ronny Drapkin, Debra L. Richardson

et al.

Cancer Treatment Reviews, Journal Year: 2022, Volume and Issue: 112, P. 102489 - 102489

Published: Nov. 14, 2022

Language: Английский

Citations

28
Identifying SOX17 as a Sensitive and Specific Marker for Ovarian and Endometrial Carcinomas DOI Open Access
Nada Shaker, Wei Chen,

W. Sinclair

et al.

Modern Pathology, Journal Year: 2023, Volume and Issue: 36(1), P. 100038 - 100038

Published: Jan. 1, 2023

Language: Английский

Citations

16
Kynurenine in IDO1high cancer cell-derived extracellular vesicles promotes angiogenesis by inducing endothelial mitophagy in ovarian cancer DOI Creative Commons
Ying Xiang, Xiaocui Zheng,

Xiaoqian Zhang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 11, 2024

Abstract Background Mitophagy, a prominent cellular homeostasis process, has been implicated in modulating endothelial cell function. Emerging evidence suggests that extracellular vesicles (EVs) participate intercellular communication, which could modulate tumor angiogenesis, hallmark of ovarian cancer (OC) progression. However, the underlying mechanisms through how EVs regulate mitophagy associated with angiogenesis during OC development remain obscure. Methods The effect cell-derived on and its correlation were explored by vitro vivo experiments. Multi-omics integration analysis was employed to identify potential regulatory mitophagy, is involved development. These insights then further corroborated additional An orthotopic mouse model constructed assess antiangiogenic therapeutic Indoleamine 2,3 dioxygenase-1 (IDO1) inhibitor. Results Cancer promoted via activation contributing growth metastasis OC. aberrantly high expression IDO1 mediated abnormal tryptophan metabolism cells secretion l -kynurenine (L-kyn)-enriched EVs, levels L-kyn isolated from both tissues patient plasma derived elevated nicotinamide adenine dinucleotide (NAD +) delivering L-kyn. Besides, upregulated sirt3 increasing acetylation modification. findings are crucial for promoting correlated angiogenesis. Notably, be suppressed inhibitor model. Conclusions Together, our unveil mechanism indicate clinical relevance EV enriched as biomarker tumorigenesis Additionally, inhibitors might become an alternative option adjuvant therapy. Graphical

Language: Английский

Citations

4
BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target DOI Creative Commons
Elena Alexandrova,

Marharyta Smal,

Domenico Di Rosa

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 4, 2025

Ovarian Cancer (OC) is the most lethal gynecological malignancy, characterized by peritoneal metastasis, directly linked to OC-related deaths. Here, interrogating CRISPR-Cas9 loss-of-function genetic screen data, we identified a list of genes essential for metastatic OC, including several well-known oncogenes (PAX8, CCNE1, WWTR1, WT1, KAT6A, MECOM, and SOX17) others whose roles in OC have not yet been explored. Protein-protein interaction analysis selected revealed presence protein network participating epigenetic regulation gene expression. For one components, BRPF1, found that its increased expression correlates with progression poor prognosis patients. Functional assays demonstrated BRPF1 inhibition significantly reduces cellular migration invasion, supporting role progression. Pharmacological blockade using small molecule inhibitors resulted reduced proliferation high-grade serous cells through mechanisms involving activation programmed cell death, cycle deregulation, enhanced DNA damage. Furthermore, transcriptional changes induced targeting showed growth inhibitory effects may be mediated deregulation PPARα signaling. The obtained results indicate represents novel potential therapeutic target treatment.

Language: Английский

Citations

0
Developing and characterising bovine decellularized extracellular matrix hydrogels to biofabricate female reproductive tissues DOI Creative Commons

Eduardo Ribes Martínez,

Y. Franko,

Roksan Franko

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

This study investigated the development and characterization of decellularized extracellular matrix (dECM) hydrogels tailored for biofabrication female reproductive tissues, specifically targeting ovarian cortex, endometrium, medulla, oviduct tissues. We aimed to evaluate cytocompatibility, biomechanical properties, overall efficacy these dECMs in promoting cell viability, proliferation, morphology using bovine model. Bovine species provide a valuable model due their accessibility from slaughterhouse offering practical alternative human samples, which are often limited availability. Additionally, tissue closely mirrors certain physiological biological characteristics humans, making it relevant translational research. Our findings revealed that exhibited high biocompatibility with embryo supporting micro vascularization cellular without need external growth factors. It is important note addition alginate was crucial maintaining structural integrity hydrogel during long-term cultures. These displayed properties mimicked native vital functional activities. The printability assessments showed dECMs, particularly those cortex achieved precision replicating intended structures, though challenges such as low porosity remained. bioprinted constructs demonstrated robust growth, over 97% viability observed by day 7, indicating suitability culture. work represented significant advancement biofabrication, demonstrating potential dECM-based creating structurally viable constructs. By tailoring each dECM match unique different we paved way more effective reliable applications medicine engineering. STATEMENT OF SIGNIFICANCE: research explores use bio-inks Ovarian endometrium essential processes. Notably, microvascularization differentiation supplemental successful bioprinting underscores complex models. represents engineering, promising new avenues medicine.

Language: Английский

Citations

0