YAP signaling orchestrates the endothelin-1-guided invadopodia formation in high-grade serous ovarian cancer DOI Open Access
Piera Tocci, Valentina Caprara, Celia Román

et al.

Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(12)

Published: Nov. 4, 2024

Abstract The high-grade serous ovarian cancer (HG-SOC) is a notoriously challenging disease, characterized by rapid peritoneal dissemination. HG-SOC cells leverage actin-rich membrane protrusions, known as invadopodia, to degrade the surrounding extracellular matrix (ECM) and invade, initiating metastatic cascade. In HG-SOC, endothelin-1 (ET-1)/endothelin A receptor (ETAR)-driven signaling coordinates invadopodia activity, however how this axis integrates pro-oncogenic routes, YAP-driven one, impacting on invadopodia-mediated ECM degradation progression, deserves deeper investigation. Herein, we observed that downstream of ET-1/ET-1R axis, RhoC Rac1 GTPases, acting intermediaries, promote de-phosphorylation nuclear accumulation YAP. Conversely, treatment with dual ETA/ETB antagonist, macitentan, inhibits ET-1-driven YAP activity. Similarly, silencing, or cell transfection dominant inactive form Rac1, restores phosphorylation. Mechanistically, ET-1R/YAP signal alliance maturation into ECM-degrading structures, indicating such ET-1R-guided protein network represents route able enhance invasive potential. At functional level, found interconnection between ET-1R/RhoC signals required for MMP-2 MMP-9 proteolytic functions, invasion, cytoskeleton architecture changes, supporting strength. patient-derived xenografts (PDX) turning-off regulators RhoC/YAP, halts colonization. ET-1R targeting, hindering weakens machinery, embodying promising therapeutic avenue prevent dissemination in HG-SOC.

Language: Английский

The tale of SOX2: Focusing on lncRNA regulation in cancer progression and therapy DOI
Peng Huang,

Feng Wen,

YiShan Li

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 344, P. 122576 - 122576

Published: March 14, 2024

Language: Английский

Citations

9
Immune evasion in ovarian cancer: implications for immunotherapy and emerging treatments DOI
Romi Gupta, Raj Kumar, Courtney A. Penn

et al.

Trends in Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Niraparib restricts intraperitoneal metastases of ovarian cancer by eliciting CD36-dependent ferroptosis DOI Creative Commons

Ning Jin,

Yiyu Qian,

Xiao-Fei Jiao

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 80, P. 103528 - 103528

Published: Feb. 3, 2025

Ovarian cancer (OC) is prone to peritoneum or omentum dissemination, thus giving rise the formidable challenge of unresectable surgery and a dismal survival rate. Although niraparib holds pivotal role in maintenance treatment OC, its effect on suppressing metastases during primary intervention remains enigmatic. Recently, we initiated prospective clinical study (NCT04507841) order evaluate therapeutic efficacy neoadjuvant monotherapy for advanced OC with homologous recombination deficiency. An analysis patient tumor burden before after showed remarkable vulnerability intraperitoneal exposure. This killing capacity was closely associated accumulation fatty acids within abdomen, which confirmed by increased susceptibility cells presence acids. In context abundant acids, elevated intracellular levels lipid peroxidation, leading subsequent cell ferroptosis p53 BRCA-independent manner. Notably, under exposure, critical acid transporter CD36 dramatically upregulated tumors, facilitating excessive uptake Pharmacological inhibition either impaired anti-tumor activity both vitro murine ID8 models. Our findings demonstrate as novel mechanism underlying regression induced niraparib, thereby offering tantalizing prospects frontline application this agent management OC.

Language: Английский

Citations

1
Genome‐wide profiling of N6‐methyladenosine‐modified pseudogene‐derived long noncoding RNAs reveals the tumour‐promoting and innate immune‐restraining function of RPS15AP12 in ovarian cancer DOI Creative Commons
Jie Xu, Yifei Ren, Jiayi Lu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Pseudogene‐derived lncRNAs are widely dysregulated in cancer. Technological advancements have facilitated the functional characterization of increasing pseudogenes cancer progression. However, association between and RNA N6‐methyladenosine (m 6 A) modification cancer, as well underlying mechanisms, remains largely unexplored. Methods We analyzed expression 12 146 comprehensively examined m A RNAs derived from them their paralogs. Through integrative analysis multi‐omics data, we explored associations pseudogene dysregulation A, identifying critical involved HGSOC Tumour promotion role RPS15AP12 its cognate parent gene was characterized by cell proliferation, transwell assays, scratch assays ovarian cells xenograft nude mice. decay were used to reveal participation decreasement lncRNA stability. Luciferase reporter performed verify that enhances RPS15A competitively binding miR‐96‐3p. Western blot phosphorylation investigate impairment towards sensors MAVS (RIG‐I MDA5), downstream p‐TBK1 p‐IRF3. Finally, ELISA explore regulatory IFN‐β expression. Results M is distributed across over a thousand pseudogenes, hypomethylation leads upregulation HGSOC. identified processed pseudogene, RPS15AP12, upregulated FTO‐mediated demethylation. growth ability metastatic capabilities (OC) via functioning competitive endogenous (ceRNA) for host gene, RPS15A, through sequestration Importantly, deletion diminishes leading anti‐tumour immune responses activating RIG‐I MDA5 p‐IRF3 levels. Conclusion Our findings expand understanding A‐modulated tumour innate immunity OC. Key Points Genome‐wide profiling reveals redistribution m6A on pseudogene‐derived redistribution‐relevant representative up‐regulated demethylation acts miRNA sponge promote RPS15AP12/RPS15A axis inhibits MDA5) levels

Language: Английский

Citations

1
Clinicopathological and prognostic factor analyses of primary fallopian tube carcinoma and high-grade serous ovarian cancer: a single-institution retrospective study DOI Creative Commons

Mengyan Tu,

Xueyan Gao,

Tianchen Guo

et al.

World Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 4, 2025

This study aimed to evaluate and compare the clinicopathologic features of primary fallopian tubal carcinoma (PFTC) high-grade serous ovarian cancer (HGSOC) explore prognostic factors these two malignant tumors. Fifty-seven patients diagnosed with PFTC from 2006 2015 60 HGSOC 2014 complete information were identified at Women's Hospital Zhejiang University. The clinicopathological surgical data collected, survival was followed for 5 years after surgery. Cox proportional risk model used analyze impact on survival. For patients, mean age 57 (range, 35–77 years). most common clinical manifestations abnormal vaginal bleeding and/or discharge (61%). A total 72% cases found early stage, 90% tumors high grade (51 cases). 51% before surgery, while rest misdiagnosed. Twenty-one relapsed. overall (OS) rate 82%. OS significantly related FIGO preoperative serum CA 125 level, lymphadenectomy, residual tumor size, appendectomy, number cycles chemotherapy. However, only stage an independent variable OS. HGSOC, 67%. laterality. size Our provides important insights into HGSOC. We as factor patients. These findings emphasize critical role accurate staging achieving a less than 1 cm during research contributes refining decision-making, supporting importance optimal outcomes, guiding personalized treatment strategies improve patient prognosis in both

Language: Английский

Citations

0
Organoid development and applications in gynecological cancers: the new stage of tumor treatment DOI Creative Commons
Yang Li, Meiying Qin, Ning Liu

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 16, 2025

Gynecologic cancers (GCs), including cervical cancer (CC), ovarian (OC), endometrial (EC), as well vulvar and vaginal cancers, represent major health threats to women, with increasing incidence rates observed globally. Conventional treatments, such surgery, radiation therapy, chemotherapy, are often hindered by challenges drug resistance recurrence, contributing high mortality rates. Organoid technology has emerged a transformative tool in research, offering vitro models that closely replicate the tumor cell architecture heterogeneity of primary cancers. Tumor-derived organoids preserve histological molecular characteristics original tumors, making them invaluable for studying biology, pathways, immune microenvironment. Furthermore, play crucial role biomarker discovery, screening, development personalized therapeutic strategies. In contrast traditional lines patient-derived xenograft (PDX) models, gynecologic accurately mirror genetic mutations specific gene expression profiles tumors. This review provides an overview recent advancements organoid highlighting their contributions understanding disease mechanisms, facilitating advancing precision medicine. It also addresses potential technology, focus on its treatment approaches GCs.

Language: Английский

Citations

0
UBE2J1 is identified as a novel plasma cell-related gene involved in the prognosis of high-grade serous ovarian cancer DOI Creative Commons

Yunjie Tian,

Ruoyu Dong,

Yingxia Guan

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 28, 2025

Immune cells within tumor tissues play important roles in remodeling the microenvironment, thus affecting progression and therapeutic response. The current study was designed to identify key markers of plasma explore their role high-grade serous ovarian cancer (HGSOC). We utilized single-cell sequencing data from Gene Expression Omnibus (GEO) database immune cell types HGSOC extract related via Seurat package. effects on prognosis were analyzed univariate Cox regression, least absolute shrinkage selection operator (LASSO) gene set variation analysis (GSVA) bulk Cancer Genome Atlas (TCGA)-HGSOC cohort. Finally, evaluated Cell Counting Kit-8 (CCK-8), Transwell, colony formation, wound healing, immunofluorescence vivo growth assays. At level, we detected a significant increase proportion samples compared that normal samples. Within tissues, these found interact with CD8 + T cells, fibroblasts endothelial cells. In addition, patients high-plasma cell-related score group had better survival rates higher epithelial‒mesenchymal transition (EMT), apoptosis scores. Moreover, LASSO regression analyses revealed ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is prognostic marker HGSOC. Further functional studies overexpression UBE2J1 promoted proliferation, invasion, migration whereas knockdown attenuated abovementioned cellular behaviors. Additionally, EMT, as evidenced by alterations protein expression levels N-cadherin, snail family transcriptional repressor 2 (Slug), Twist BHLH transcription factor 1 (Twist 1) E-cadherin. silencing able inhibit vivo. Overall, this elucidated novel oncogene HGSOC, uncovering new mechanisms tumorigenesis promising targets for patients.

Language: Английский

Citations

0
PLIN2 Promotes Lipid Accumulation in Ascites‐Associated Macrophages and Ovarian Cancer Progression by HIF1α/SPP1 Signaling DOI Creative Commons
Hui Luo,

Xiaoling She,

Yubo Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

A major characteristic of ovarian cancer (OC) is its unique route metastasis via ascites. The immune microenvironment in ascites remains understudied, leaving the mechanism ascites-mediated abdominal obscure. Here, a single-cell transcriptomic landscape CD45+ cells across multiple anatomical sites depicted, including primary tumors, metastatic lesions, and ascites, from patients diagnosed with high-grade serous carcinoma (HGSOC). novel subset perilipin 2 high (PLIN2hi) macrophages are identified that enriched positively correlated OC progression, hence being designated as "ascites-associated (AAMs)". AAMs lipid-loaded overexpression lipid droplet protein PLIN2. Overexpression or suppression PLIN2 can enhance inhibit tumor cell migration, invasion, vascular permeability vitro, which also confirmed vivo. Mechanistically, it demonstrated boosts HIF1α/SPP1 signaling macrophages, thereby exerting pro-tumor functions. Finally, PLIN2-targeting liposome designed to efficiently suppress production metastasis. Taken together, this work provides comprehensive characterization cancer-promoting function lipid-rich property ascites-enriched PLIN2hi establishes link between metabolism hypoxia within context microenvironment, elucidates pivotal role trans-coelomic OC.

Language: Английский

Citations

0
Establishment and Its Utility of a Patient-Derived Cell Xenografts (PDCX) Model with Cryopreserved Cancer Cells from Human Tumor DOI Creative Commons

Ki Yeon Kim,

Ji Min Lee, Eun Ji Lee

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 325 - 325

Published: Feb. 21, 2025

Patient-derived xenograft (PDX) models are powerful tools in cancer research, offering an accurate platform for evaluating treatment efficacy and predicting responsiveness. However, these necessitate surgical techniques tumor tissue transplantation face challenges with non-uniform growth among animals. To address issues, we attempted to develop a new PDX modeling method using high-grade serous ovarian (HGSC), fatal disease 5-year survival rate of 29%, which requires personalized research due its morphological, genetic, molecular heterogeneities. In this study, developed patient-derived cell (PDCX) model high engraftment efficiency (64%) that utilizes primary cells instead patient tissues. Primary can be stably cryopreserved extended periods (up 485 days), when transplanted into female NSGA mice, they maintain morphological characteristics without significant genetic differences compared their original tumors. Furthermore, PDCX easily produced syringe, allowing uniform sizes across multiple Additionally, M2 PDCXs exhibited significantly faster PDTXs. Consequently, our offers streamlined approach treatments minimal experimental variability.

Language: Английский

Citations

0
Fertility Sparing Surgery Upon Reproductive and Oncologic results in Ovarian Cancer patients Stage I (FIGO): A Systematic Review DOI Creative Commons

Stylianos Sergios Chatziioannou,

Chrisostomos Sofoudis

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Purpose This systematic review evaluates the oncologic and reproductive outcomes of fertility-sparing surgery (FSS) in women diagnosed with stage I ovarian cancer, as classified by International Federation Gynecology Obstetrics (FIGO). The goal is to assess safety effectiveness FSS preserving fertility without compromising survival outcomes. Methods A search was conducted MEDLINE (PubMed), SCOPUS, Google Scholar for studies published English from 2014 onward. Studies involving under 50 cancer who opted were included. Data extraction focused on (recurrence rates) (pregnancy live birth rates). Study selection followed PRISMA guidelines. Results Seventeen comprising 1030 patients met inclusion criteria. Pregnancy success rates ranged 25–91.3%, exceeding 80% most studies. Spontaneous conception predominant, though 3.7–28% required assisted technologies (ART). Despite 58% expressing a desire future pregnancy, only 13% actively attempted conception. Recurrence varied 3–33.3%, reporting between 8% 15%. Overall 88–100%, disease-free remained above 90%. highest recurrence observed mucinous carcinoma FIGO Stage IC2/IC3 subtypes. Conclusion viable alternative radical carefully selected patients, favorable However, risks challenges highlight need multidisciplinary counseling, long-term surveillance, further research refine criteria optimize preservation techniques.

Language: Английский

Citations

0