Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

The Landscape of Exosomes Biogenesis to Clinical Applications.

Exosomes are extracellular vesicles that originate from various cells and mediate intercellular communication, altering the behavior or fate of recipient cells. They carry diverse macromolecules, such as lipids, proteins, carbohydrates, and nucleic acids. Environmental stressors can change the exosomal contents of many cells, making them useful for diagnosing many chronic disorders, especially neurodegenerative, cardiovascular, cancerous, and diabetic diseases. Moreover, exosomes can be engineered as therapeutic agents to modulate disease processes. State-of-art techniques are employed to separate exosomes including ultracentrifugation, size-exclusion chromatography and immunoaffinity. However, modern technologies such as aqueous two-phase system as well as microfluidics are gaining attention in the recent years. The article highlighted the composition, biogenesis, and implications of exosomes, as well as the standard and novel methods for isolating them and applying them as biomarkers and therapeutic cargo carriers.

A resource-based mechanistic framework for castration-resistant prostate cancer (CRPC).

Cancer therapy often leads to the selective elimination of drug-sensitive cells from the tumour. This can favour the growth of cells resistant to the therapeutic agent, ultimately causing a tumour relapse. Castration-resistant prostate cancer (CRPC) is a well-characterised instance of this phenomenon. In CRPC, after systemic androgen deprivation therapy (ADT), a subset of drug-resistant cancer cells autonomously produce testosterone, thus enabling tumour regrowth. A previous theoretical study has shown that such a tumour relapse can be delayed by inhibiting the growth of drug-resistant cells using biotic competition from drug-sensitive cells. In this context, the centrality of resource dynamics to intra-tumour competition in the CRPC system indicates clear scope for the construction of theoretical models that can explicitly incorporate the underlying mechanisms of tumour ecology. In the current study, we use a modified logistic framework to model cell-cell interactions in terms of the production and consumption of resources. Our results show that steady state composition of CRPC can be understood as a composite function of the availability and utilisation efficiency of two resources-oxygen and testosterone. In particular, we show that the effect of changing resource availability or use efficiency is conditioned by their general abundance regimes. Testosterone typically functions in trace amounts and thus affects steady state behaviour of the CRPC system differently from oxygen, which is usually available at higher levels. Our data thus indicate that explicit consideration of resource dynamics can produce novel and useful mechanistic understanding of CRPC. Furthermore, such a modelling approach also incorporates variables into the system's description that can be directly measured in a clinical context. This is therefore a promising avenue of research in cancer ecology that could lead to therapeutic approaches that are more clearly rooted in the biology of CRPC.

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model.

Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.

Cell-cell communication in stem cells and cancer: Alone but in touch.

BACKGROUND: Cellular communication and signaling pathways are fundamental regulators of stem cell and cancer cell behaviors. This review explores the intricate interplay of these pathways in governing cellular behaviors, focusing on their implications for diseases, particularly cancer. OBJECTIVES: This comprehensive review aims to elucidate the significance of cellular signaling pathways in regulating the behavior of stem cells and cancer cells. It delves into the alterations in these pathways, their impact on cell fate, and their implications for developing diseases, notably cancer. The objective is to underscore the importance of understanding these signaling pathways for developing targeted therapeutic strategies. METHODS: The review critically analyzes existing literature and research findings concerning the roles of signaling pathways in stem cell behavior regulation, emphasizing their parallels and disparities in cancer cells. It synthesizes information on both direct and indirect modes of cell communication to delineate the complexity of signaling networks. RESULTS: Direct and indirect modes of cell communication intricately regulate the complex signaling pathways governing stem cell behaviors, influencing differentiation potential and tissue regeneration. Alterations in these pathways significantly impact stem cell fate, contributing to disease pathogenesis, including cancer. Understanding these signaling cascades offers insights into developing targeted therapies, particularly cancer treatment. CONCLUSION: Understanding the regulation of signaling pathways in stem cells and the specialized subset of cancer stem cells holds promise for innovative therapeutic approaches. By targeting aberrant signaling pathways, tailored interventions may improve treatment outcomes. This review underscores the critical role of signaling pathways in cellular behaviors, offering a pathway toward developing novel, more effective therapies for diverse diseases and disorders.

The epithelial polarity axis controls the resting membrane potential and Cl- co-transport in breast glandular structures.

The membrane potential (MP) controls cell homeostasis by directing molecule transport and gene expression. How the MP is set upon epithelial differentiation is unknown. Given that tissue architecture also controls homeostasis, we investigated the relationship between basoapical polarity and resting MP in three-dimensional culture of the HMT-3522 breast cancer progression. A microelectrode technique to measure MP and input resistance reveals that the MP is raised by gap junction intercellular communication (GJIC), which directs tight-junction mediated apical polarity, and is decreased by the Na+/K+/2Cl- (NKCC, encoded by SLC12A1 and SLC12A2) co-transporter, active in multicellular structures displaying basal polarity. In the tumor counterpart, the MP is reduced. Cancer cells display diminished GJIC and do not respond to furosemide, implying loss of NKCC activity. Induced differentiation of cancer cells into basally polarized multicellular structures restores widespread GJIC and NKCC responses, but these structures display the lowest MP. The absence of apical polarity, necessary for cancer onset, in the non-neoplastic epithelium is also associated with the lowest MP under active Cl- transport. We propose that the loss of apical polarity in the breast epithelium destabilizes cellular homeostasis in part by lowering the MP.

Mutation of p53 increases the competitive ability of pluripotent stem cells.

During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development.

Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.

Connexins and pannexins are transmembrane proteins that can form direct (gap junctions) or indirect (connexons, pannexons) intercellular communication channels. By propagating ions, metabolites, sugars, nucleotides, miRNAs, and/or second messengers, they participate in a variety of physiological functions, such as tissue homeostasis and host defense. There is solid evidence supporting a role for intercellular signaling in various pulmonary inflammatory diseases where alteration of connexin/pannexin channel functional expression occurs, thus leading to abnormal intercellular communication pathways and contributing to pathophysiological aspects, such as innate immune defense and remodeling. The integrity of the airway epithelium, which is the first line of defense against invading microbes, is established and maintained by a repair mechanism that involves processes such as proliferation, migration, and differentiation. Here, we briefly summarize current knowledge on the contribution of connexins and pannexins to necessary processes of tissue repair and speculate on their possible involvement in the shaping of the airway epithelium integrity.

Polarization and motility of one-dimensional multi-cellular trains.

Collective cell migration, whereby cells adhere to form multi-cellular clusters that move as a single entity, play an important role in numerous biological processes, such as during development and cancer progression. Recent experimental work focused on migration of one-dimensional cellular clusters, confined to move along adhesive lanes, as a simple geometry in which to systematically study this complex system. One-dimensional migration also arises in the body when cells migrate along blood vessels, axonal projections, and narrow cavities between tissues. We explore here the modes of one-dimensional migration of cellular clusters ("trains") by implementing cell-cell interactions in a model of cell migration that contains a mechanism for spontaneous cell polarization. We go beyond simple phenomenological models of the cells as self-propelled particles by having the internal polarization of each cell depend on its interactions with the neighboring cells that directly affect the actin polymerization activity at the cell's leading edges. Both contact inhibition of locomotion and cryptic lamellipodia interactions between neighboring cells are introduced. We find that this model predicts multiple motility modes of the cell trains, which can have several different speeds for the same polarization pattern. Compared to experimental data, we find that Madin-Darby canine kidney cells are poised along the transition region where contact inhibition of locomotion and cryptic lamellipodia roughly balance each other, where collective migration speed is most sensitive to the values of the cell-cell interaction strength.

Insulin regulates gap junction intercellular communication in porcine granulosa cells through modulation of connexin43 protein expression.

Gap junction intercellular communication (GJIC) among granulosa cells plays an important role in folliculogenesis, and it is temporal-spatially regulated during follicular development. Connexin (Cx) proteins predominantly form the basal structure of gap junctions in granulosa cells. In our study, immunohistochemical analysis revealed that Cx43 is the most widely expressed connexin in porcine follicles, especially among the large antral follicles. With application of insulin on porcine granulosa cells, we found that insulin significantly facilitated the protein level of Cx43, not mRNA level. This process is dependent on the phosphorylated activities of AKT and Erk since selective AKT and Erk inhibitors, LY294002 and U0126, respectively, hampered the potential of insulin to up-regulate Cx43 protein expression. As a consequence, the insulin-enhanced Cx43-couple GJIC activity in porcine granulosa cells was corresponding attenuated by the administration of LY294002 and U0126. Our findings provide a new insight into the molecular mechanisms by which insulin mediates cell-cell communication in porcine granulosa cells and sheds light on nutrition-reproduction interactions.

Reprogramming of connexin landscape fosters fast gap junction intercellular communication in human papillomavirus-infected epithelia.

Human papillomaviruses (HPVs) are highly prevalent commensal viruses that require epithelial stratification to complete their replicative cycle. While HPV infections are most often asymptomatic, certain HPV types can cause lesions, that are usually benign. In rare cases, these infections may progress to non-replicative viral cycles associated with high HPV oncogene expression promoting cell transformation, and eventually cancer when not cleared by host responses. While the consequences of HPV-induced transformation on keratinocytes have been extensively explored, the impact of viral replication on epithelial homeostasis remains largely unexplored. Gap junction intercellular communication (GJIC) is critical for stratified epithelium integrity and function. This process is ensured by a family of proteins named connexins (Cxs), including 8 isoforms that are expressed in stratified squamous epithelia. GJIC was reported to be impaired in HPV-transformed cells, which was attributed to the decreased expression of the Cx43 isoform. However, it remains unknown whether and how HPV replication might impact on the expression of Cx isoforms and GJIC in stratified squamous epithelia. To address this question, we have used 3D-epithelial cell cultures (3D-EpCs), the only model supporting the productive HPV life cycle. We report a transcriptional downregulation of most epithelial Cx isoforms except Cx45 in HPV-replicating epithelia. At the protein level, HPV replication results in a reduction of Cx43 expression while that of Cx45 increases and displays a topological shift toward the cell membrane. To quantify GJIC, we pioneered quantitative gap-fluorescence loss in photobleaching (FLIP) assay in 3D-EpCs, which allowed us to show that the reprogramming of Cx landscape in response to HPV replication translates into accelerated GJIC in living epithelia. Supporting the pathophysiological relevance of our observations, the HPV-associated Cx43 and Cx45 expression pattern was confirmed in human cervical biopsies harboring HPV. In conclusion, the reprogramming of Cx expression and distribution in HPV-replicating epithelia fosters accelerated GJIC, which may participate in epithelial homeostasis and host immunosurveillance.

Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas.

Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, and immune system regulation, as well as contributing to tumor progression and neurodegenerative diseases pathology. Recent studies have shown that gliomas secrete a panel of exosomes which have been associated with cell invasion and migration, tumor immune tolerance, potential for malignant transformation, neovascularization, and resistance to treatment. Exosomes have therefore emerged as intercellular communicators, which mediate the tumor-microenvironment interactions and exosome-regulated glioma cell stemness and angiogenesis. They may induce tumor proliferation and malignancy in normal cells by carrying pro-migratory modulators from cancer cells as well as many different molecular cancer modifiers, such as oncogenic transcripts, miRNAs, mutant oncoproteins, etc., which promote the communication of cancer cells with the surrounding stromal cells and provide valuable information on the molecular profile of the existing tumor. Moreover, engineered exosomes can provide an alternative system for drug delivery and enable efficient treatment. In the present review, we discuss the latest findings regarding the role of exosomes in glioma pathogenesis, their utility in non-invasive diagnosis, and potential applications to treatment.

CX43 down-regulation promotes cell aggressiveness and 5-fluorouracil-resistance by attenuating cell stiffness in colorectal carcinoma.

Chemotherapy is one of the most commonly treatments of advanced colorectal cancer (CRC). However, the drug resistant following chemotherapeutic treatment is a significant challenge in the clinical management of CRC. Therefore, understanding the resistance mechanisms and developing new strategies for enhancing the sensitivity are urgently needed to improve CRC outcome. Connexins contribute to the formation of gap junctions among neighboring cells and then advance gap junctional intercellular communication (GJIC) for transportation of ions and small molecules. Although the drug resistance resulted from GJIC dysfunctional by aberrant expression of connexins is relatively well understood, the underlying mechanisms of mechanical stiffness mediated by connexin responsible for chemoresistance are largely unknown in CRC. Here, we demonstrated that connexin 43 (CX43) expression was downregulated in CRC and that loss of CX43 expression was positively correlated with metastasis and poor prognosis of CRC patients. The CX43 overexpressing suppressed CRC progression and increased the sensitivity to 5-fluorouracil (5-FU) via enhanced GJIC in vitro and in vivo. Moreover, we also highlight that the downregulation of CX43 in CRC increases the stemness of cells via reducing the cell stiffness, thus promoting the drug resistance. Our results further suggest that both effects, that is changes in the mechanical stiffness of the cell and GJIC mediated by CX43 deregulated, are closely related to drug resistance in CRC, which indicating CX43 as a target against cancer growth and chemoresistance in CRC.

Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture.

Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the 'transferome') is unknown. Here, we analyzed the transferome in an in vitro human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically,<1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.

The role of extracellular vesicles in cancer.

Intercellular communication is a key feature of cancer progression and metastasis. Extracellular vesicles (EVs) are generated by all cells, including cancer cells, and recent studies have identified EVs as key mediators of cell-cell communication via packaging and transfer of bioactive constituents to impact the biology and function of cancer cells and cells of the tumor microenvironment. Here, we review recent advances in understanding the functional contribution of EVs to cancer progression and metastasis, as cancer biomarkers, and the development of cancer therapeutics.

Extracellular vesicles as a new horizon in the diagnosis and treatment of inflammatory eye diseases: A narrative review of the literature.

Extracellular vesicles include exosomes, microvesicles, and apoptotic bodies. Their cargos contain a diverse variety of lipids, proteins, and nucleic acids that are involved in both normal physiology and pathology of the ocular system. Thus, studying extracellular vesicles may lead to a more comprehensive understanding of the pathogenesis, diagnosis, and even potential treatments for various diseases. The roles of extracellular vesicles in inflammatory eye disorders have been widely investigated in recent years. The term "inflammatory eye diseases" refers to a variety of eye conditions such as inflammation-related diseases, degenerative conditions with remarkable inflammatory components, neuropathy, and tumors. This study presents an overview of extracellular vesicles' and exosomes' pathogenic, diagnostic, and therapeutic values in inflammatory eye diseases, as well as existing and potential challenges.

Independent Innexin Radiation Shaped Signaling in Ctenophores.

Innexins facilitate cell-cell communication by forming gap junctions or nonjunctional hemichannels, which play important roles in metabolic, chemical, ionic, and electrical coupling. The lack of knowledge regarding the evolution and role of these channels in ctenophores (comb jellies), the likely sister group to the rest of animals, represents a substantial gap in our understanding of the evolution of intercellular communication in animals. Here, we identify and phylogenetically characterize the complete set of innexins of four ctenophores: Mnemiopsis leidyi, Hormiphora californensis, Pleurobrachia bachei, and Beroe ovata. Our phylogenetic analyses suggest that ctenophore innexins diversified independently from those of other animals and were established early in the emergence of ctenophores. We identified a four-innexin genomic cluster, which was present in the last common ancestor of these four species and has been largely maintained in these lineages. Evidence from correlated spatial and temporal gene expression of the M. leidyi innexin cluster suggests that this cluster has been maintained due to constraints related to gene regulation. We describe the basic electrophysiological properties of putative ctenophore hemichannels from muscle cells using intracellular recording techniques, showing substantial overlap with the properties of bilaterian innexin channels. Together, our results suggest that the last common ancestor of animals had gap junctional channels also capable of forming functional innexin hemichannels, and that innexin genes have independently evolved in major lineages throughout Metazoa.

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal-fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal-fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies. The adoptive transfer of Tim-3+Mφs, rather than Tim-3-Mφs, reversed the murine placental dysplasia resulting from Mφ depletion. With the higher production of angiogenic growth factors (AGFs, including PDGF-AA, TGF-α, and VEGF), Tim-3+dMφs were more beneficial in promoting the invasion and tube formation ability of trophoblasts. The blockade of AGFs in Tim-3+Mφs led to the narrowing of the labyrinthine layer of the placenta, compromising maternal-fetal tolerance, and increasing the risk of fetal loss. Meanwhile, the AGFs-treated Tim-3-Mφs could resolve the placental dysplasia and fetal loss resulting from Mφ depletion. These findings emphasized the vital roles of Tim-3 in coordinating Mφs-extravillous trophoblasts interaction via AGFs to promote pregnancy maintenance and in extending the role of checkpoint signaling in placental development. The results obtained in our study also firmly demonstrated that careful consideration of reproductive safety should be taken when selecting immune checkpoint and AGF blockade therapies in real-world clinical care.

Connexin 43 trafficking and regulation of gap junctional intercellular communication alters ovarian cancer cell migration and tumorigenesis.

Ovarian cancer persists to be the most lethal gynecological malignancy, demanding rigorous treatments involving radio-chemotherapy that trigger toxicity and consequently mortality among patients. An improved understanding of the disease progression may pioneer curative therapies. Mouse epithelial ovarian cancer cell lines, ID8 and ID8-VEGF (overexpressing VEGF) were intraperitoneally injected in C57BL/6 female mice to develop a Syngeneic Ovarian cancer mouse model. It was observed that ID8-VEGF cells were able to induce aggressive tumor growth in mice compared to ID8 cells. Furthermore, results of the current in vitro study comparing ID8 and ID8-VEGF demonstrated that highly tumorigenic ID8-VEGF had reduced gap junctional intercellular communication (GJIC) due to intracellular Connexin 43 (Cx43) expression. Additionally, ID8 cells with reduced tumorigenic capability expressed significant GJIC. Furthermore, loss of GJIC in ID8-VEGF cells induced shorter tunneling nanotube formations, while ID8 cells develops longer tunneling nanotube to maintain cellular crosstalk. The administration of a pharmacological drug 4-phenylbutyrate (4PBA) ensured the restoration of GJIC in both the ovarian cancer cell lines. Additionally, 4PBA treatment significantly inhibited the migration of ovarian cancer cell lines and tumor formation in ovarian cancer mice models. In summary, the 4PBA-mediated restoration of GJIC suppressed migration (in vitro) and tumorigenesis (in vivo) of ovarian cancer cells. The present study suggests that Cx43 assembled GJIC and its supportive signaling pathways are a prospective target for restricting ovarian cancer progression.