American journal of physiology. Cell physiology最新文献

{"title":"Metabolic T-cell phenotypes: from bioenergetics to function.","authors":"Nouria Jantz-Naeem, Nese Guvencli, Romy Böttcher-Loschinski, Martin Böttcher, Dimitrios Mougiakakos, Sascha Kahlfuss","doi":"10.1152/ajpcell.00478.2024","DOIUrl":"10.1152/ajpcell.00478.2024","url":null,"abstract":"<p><p>It is well known that T-cell metabolism and function are intimately linked. Metabolic reprogramming is a dynamic process that provides the necessary energy and biosynthetic precursors while actively regulating the immune response of T cells. As such, aberrations and dysfunctions in metabolic (re)programming, resulting in altered metabolic endotypes, may have an impact on disease pathology in various contexts. With the increasing demand for personalized and highly specialized medicine and immunotherapy, understanding metabolic profiles and T-cell subset dependence on specific metabolites will be crucial to harness the therapeutic potential of immunometabolism and T cell bioenergetics. In this review, we dissect metabolic alterations in different T-cell subsets in autoimmune and viral inflammation, T cell and non-T-cell malignancies, highlighting potential anchor points for future treatment and therapeutic exploitation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1062-C1075"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of TGF-β/SMAD/YAP/TAZ signaling in skeletal muscle fibrosis.","authors":"Felipe S Gallardo, Meilyn Cruz-Soca, Alexia Bock-Pereda, Jennifer Faundez-Contreras, Cristian Gutiérrez-Rojas, Alessandro Gandin, Veronica Torresan, Juan Carlos Casar, Andrea Ravasio, Enrique Brandan","doi":"10.1152/ajpcell.00541.2024","DOIUrl":"10.1152/ajpcell.00541.2024","url":null,"abstract":"<p><p>Skeletal muscle fibrosis is strongly associated with the differentiation of its resident multipotent fibro/adipogenic progenitors (FAPs) toward the myofibroblast phenotype. Although transforming growth factor type β (TGF-β) signaling is well-known for driving FAPs differentiation and fibrosis, due to its pleiotropic functions its complete inhibition is not suitable for treating fibrotic disorders such as muscular dystrophies. Here, we describe that TGF-β operates through the mechanosensitive transcriptional regulators Yes-associated protein (YAP)/ transcriptional coactivator with PDZ-binding motif (TAZ) to determine the myofibroblast fate of FAPs and skeletal muscle fibrosis. Spatial transcriptomics analyses of dystrophic and acute injured muscles showed that areas with active fibrosis and TGF-β signaling displayed high YAP/TAZ activity. Using a TGF-β-driven fibrotic mouse model, we found that activation of YAP/TAZ in activated FAPs is associated with the fibrotic process. Mechanistically, primary culture of FAPs reveals the remarkable ability of TGF-β1 to activate YAP/TAZ through its canonical SMAD3 pathway. Moreover, inhibition of YAP/TAZ, either by disrupting its activity (with Verteporfin) or cellular mechanotransduction (with the Rho inhibitor C3 or soft matrices), decreased TGF-β1-dependent FAPs differentiation into myofibroblasts. In vivo, administration of Verteporfin in mice limits the deposition of collagen and fibronectin, and the activation of FAPs during the development of fibrosis. Overall, our work provides robust evidence for considering YAP/TAZ as a potential target in muscular fibroproliferative disorders.<b>NEW & NOTEWORTHY</b> The understanding of the nuclear factors governing the differentiation of muscular fibro/adipogenic progenitors (FAPs) into myofibroblasts is in its infancy. Here, we comprehensively elucidate the status, regulation, and role of the mechanotransducers Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) in the muscular fibrotic process. Our findings reveal that inhibiting cellular mechanotransduction limits FAP differentiation and the extent of muscular fibrosis exerted by transforming growth factor type β (TGF-β). This research shed new lights on the molecular mechanisms dictating the cell fate of FAPs and the muscular fibrosis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1015-C1028"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRE1 is a promising therapeutic target in pancreatic cancer.","authors":"Denise Lucas, Tamal Sarkar, Clara Y Niemeyer, Julian C Harnoss, Martin Schneider, Moritz J Strowitzki, Jonathan M Harnoss","doi":"10.1152/ajpcell.00551.2024","DOIUrl":"10.1152/ajpcell.00551.2024","url":null,"abstract":"<p><p>[Figure: see text].</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C806-C824"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hunting glioblastoma recurrence: glioma stem cells as retrospective targets.","authors":"Sümeyra Mengüç Emir, Birnur Sinem Karaoğlan, Ramazan Kaşmer, Hilal Buse Şirin, Batuhan Sarıyıldız, Nihal Karakaş","doi":"10.1152/ajpcell.00344.2024","DOIUrl":"10.1152/ajpcell.00344.2024","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain malignancies in adults. Standard approaches, including surgical resection followed by adjuvant radio- and chemotherapy with temozolomide (TMZ), provide only transient control, as GBM frequently recurs due to its infiltrative nature and the presence of therapy-resistant subpopulations such as glioma stem cells (GSCs). GSCs, with their quiescent state and robust resistance mechanisms, evade conventional therapies, contributing significantly to relapse. Consequently, current treatment methods for GBM face significant limitations in effectively targeting GSCs. In this review, we emphasize the relationship between GBM recurrence and GSCs, discuss the current limitations, and provide future perspectives to overwhelm the challenges associated with targeting GSCs. Eliminating GSCs may suppress recurrence, achieve durable responses, and improve therapeutic outcomes for patients with GBM.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1045-C1061"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What are the potential mechanisms of fatigue-induced skeletal muscle hypertrophy with low-load resistance exercise training?","authors":"Luke D Flewwelling, Sarkis J Hannaian, Victor Cao, Thomas Chaillou, Tyler A Churchward-Venne, Arthur J Cheng","doi":"10.1152/ajpcell.00266.2024","DOIUrl":"10.1152/ajpcell.00266.2024","url":null,"abstract":"<p><p>High-load resistance exercise (>60% of 1-repetition maximum) is a well-known stimulus to enhance skeletal muscle hypertrophy with chronic training. However, studies have intriguingly shown that low-load resistance exercise training (RET) (≤60% of 1-repetition maximum) can lead to similar increases in skeletal muscle hypertrophy as compared with high-load RET. This has raised questions about the underlying mechanisms for eliciting the hypertrophic response with low-load RET. A key characteristic of low-load RET is performing resistance exercise to, or close to, task failure, thereby inducing muscle fatigue. The primary aim of this evidence-based narrative review is to explore whether muscle fatigue may act as an indirect or direct mechanism contributing to skeletal muscle hypertrophy during low-load RET. It has been proposed that muscle fatigue could indirectly stimulate muscle hypertrophy through increased muscle fiber recruitment, mechanical tension, ultrastructural muscle damage, the secretion of anabolic hormones, and/or alterations in the expression of specific proteins involved in muscle mass regulation (e.g., myostatin). Alternatively, it has been proposed that fatigue could directly stimulate muscle hypertrophy through the accumulation of metabolic by-products (e.g., lactate), and/or inflammation and oxidative stress. This review summarizes the existing literature eluding to the role of muscle fatigue as a stimulus for low-load RET-induced muscle hypertrophy and provides suggested avenues for future research to elucidate how muscle fatigue could mediate skeletal muscle hypertrophy.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1001-C1014"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor metabolism as a factor affecting diversity in cancer cachexia.","authors":"Oliver F Bathe","doi":"10.1152/ajpcell.00677.2024","DOIUrl":"10.1152/ajpcell.00677.2024","url":null,"abstract":"<p><p>Cancer cachexia is a multifaceted metabolic syndrome characterized by muscle wasting, fat redistribution, and metabolic dysregulation, commonly associated with advanced cancer but sometimes also evident in early-stage disease. More subtle body composition changes have also been reported in association with cancer, including sarcopenia, myosteatosis, and increased fat radiodensity. Emerging evidence reveals that body composition changes including sarcopenia, myosteatosis, and increased fat radiodensity, arise from distinct biological mechanisms and significantly impact survival outcomes. Importantly, these features often occur independently, with their combined presence exacerbating poor prognoses. Tumor plays a pivotal role in driving these host changes, either by acting as a metabolic parasite or by releasing mediators that disrupt normal tissue function. This review explores the diversity of tumor metabolism. It highlights the potential for tumor-specific metabolic phenotypes to influence systemic effects, including fat redistribution and sarcopenia. Addressing this tumor-host metabolic interplay requires personalized approaches that disrupt tumor metabolism while preserving host health. Promising strategies include targeted pharmacological interventions and anticachexia agents like growth differentiation factor 15 (GDF-15) inhibitors. Nutritional modifications such as ketogenic diets and omega-3 fatty acid supplementation also merit further investigation. In addition to preserving muscle, these therapies will need to be evaluated for their capability to improve survival and quality of life. This review underscores the need for further research into tumor-driven metabolic effects on the host and the development of integrative treatment strategies to address the interconnected challenges of cancer progression and cachexia.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C908-C920"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-induced PFKFB3-mediated glycolysis promoting myometrium contraction through the PI3K-Akt-mTOR pathway in preterm birth mice.","authors":"Jing He, Xuan Li, Huihui Yu, Chenyi Xu, Ruixian Tian, Ping Zhou, Zongzhi Yin","doi":"10.1152/ajpcell.00704.2024","DOIUrl":"10.1152/ajpcell.00704.2024","url":null,"abstract":"<p><p>Inflammation is a significant risk factor for preterm birth. Inflammation enhances glycolytic processes in various cell types and contributes to the development of myometrial contractions. However, the potential of inflammation to activate glycolysis in pregnant murine uterine smooth muscle cells (mUSMCs) and its role in promoting inflammatory preterm birth remain unexplored. In this study, lipopolysaccharide was employed to establish both cell and animal inflammation models. We found that inflammation of mUSMCs during late pregnancy could initiate glycolysis and promote cell contraction. Subsequently, the inhibition of glycolysis using the glycolysis inhibitor 2-deoxyglucose can reverse inflammation-induced cell contraction. The expression of 6-phosphofructokinase 2 kinase (PFKFB3) was significantly upregulated in mUSMCs following lipopolysaccharide stimulation. In addition, lactate accumulation and enhanced contraction were observed. Inhibition of PFKFB3 reversed the lactate accumulation and enhanced contraction induced by inflammation. We also found that inflammation activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of the rapamycin (mTOR) pathway, leading to the upregulation of PFKFB3 expression. The PI3K-Akt pathway inhibitor LY294002 and the mTOR pathway inhibitor rapamycin effectively inhibited the upregulation of PFKFB3 protein expression, lactate production, and the enhancement of cell contraction induced by lipopolysaccharide. This study indicates that inflammation regulates PFKFB3 through the PI3K-Akt-mTOR pathway, which enhances the glycolytic process in pregnant mUSMCs, ultimately leading to myometrial contraction.<b>NEW & NOTEWORTHY</b> Expression of PFKFB3, a key enzyme in glycolysis, was significantly upregulated both in the mUSMCs and myometrium of mice during late pregnancy after lipopolysaccharide stimulation. Activation of the PI3K-Akt-mTOR pathway enhanced PFKFB3 expression, which is involved in the initiation of glycolysis. Inflammation-activated PFKFB3 via the PI3K-Akt-mTOR pathway, which enhances the cellular glycolytic process and thus promotes myometrium contraction in pregnancy.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C895-C907"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen sulfide-mediated inhibition of ROCK₂ exerts a vasoprotective effect on ischemic brain injury.","authors":"Ye Chen, Fangfang Xu, Fang Chen, Shuaishuai Li, Miao Wu, Shuo Chen, Jinhua Chen, Zhaoyi Yang, Zhongwu Sun, Zhiwu Chen","doi":"10.1152/ajpcell.00708.2024","DOIUrl":"10.1152/ajpcell.00708.2024","url":null,"abstract":"<p><p>As a gas molecule, hydrogen sulfide (H₂S) exerts neuroprotective effects. Despite its recognized importance, there remains a need for a deeper understanding of H₂S's impact on vascular smooth muscle cells and its role in ischemic brain injury. This study employs encompassing cultured primary cerebral vascular smooth muscle cells, oxygen-glucose deprivation/reoxygenation model, in vitro vascular tone assessments, in vivo middle cerebral artery occlusion and reperfusion experimentation in male rats, and the utilization of Rho-associated coiled-coil containing protein kinase 2 (<i>ROCK₂</i>) knockout, to unravel the intricate relationship between H₂S and cerebrovascular diastolic function. Our findings show that RhoA activation induces heightened vascular smooth muscle cell (VSMC) contraction, whereas the introduction of exogenous H₂S mitigates the relaxant effect of the middle cerebral artery in rats through the downregulation of both ROCK₁ and ROCK₂, with ROCK₂ exhibiting a more pronounced effect. Correspondingly, the attenuation of ROCK₂ expression yields a more substantial reduction in the protective impact of H₂S on cerebral blood flow, as well as learning and memory ability in ischemic injury, compared with the decrease in ROCK₁ expression. Moreover, we demonstrate that H₂S effectively mitigates the damage induced by oxygen-glucose deprivation/reoxygenation in male mouse primary vascular smooth muscle cells. This effect is characterized by enhanced cell proliferation, reduced lactate dehydrogenase leakage, elevated superoxide dismutase activity, and inhibited apoptosis. Notably, this protective effect is markedly diminished in cells derived from ROCK₂ knockout mice. Our study reveals that H₂S can relax cerebral vascular smooth muscle and ameliorate ischemic stroke injury by inhibiting the ROCK, with a particular emphasis on the role of ROCK₂.<b>NEW & NOTEWORTHY</b> This study employs a diverse array of methods; our collective findings indicate that H₂S safeguards against ischemic brain injury by inhibiting ROCK activity, thereby promoting relaxation of cerebral smooth muscle and mitigating the impairment of cerebral smooth muscle cell function caused by oxygen-glucose deprivation/reoxygenation. In addition, our data underscore the critical role of ROCK₂ in mediating the cerebral protective effects of H₂S, surpassing that of ROCK₁.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C986-C1000"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota protect against frailty and loss of skeletal muscle, and maintain inflammatory tone during aging in mice.","authors":"Meghan O Conn, Erica N DeJong, Daniel M Marko, Russta Fayyazi, Dana Kukje Zada, Kevin P Foley, Nicole G Barra, Dawn M E Bowdish, Jonathan D Schertzer","doi":"10.1152/ajpcell.00869.2024","DOIUrl":"10.1152/ajpcell.00869.2024","url":null,"abstract":"<p><p>Chronic low-level inflammation or \"inflammaging\" is hypothesized to contribute to sarcopenia and frailty. Resident microbiota are thought to promote inflammaging, frailty, and loss of skeletal muscle mass. We tested immunity and frailty in male C57BL6/N germ-free (GF), specific pathogen-free (SPF) mice, and mice that were born germ-free and colonized (COL) with an SPF microbiota. Male and female GF mice had lower systemic cellular inflammation indicated by lower blood Ly6C^high monocytes across their lifespan. Male GF mice had lower body mass, but relative to body mass, GF mice had smaller hindlimb muscles and smaller muscle fibers compared with SPF mice across the lifespan. Male and female GF mice had increased frailty at 18 mo or older. Colonization of female GF mice increased blood Ly6C^high monocytes but did not affect frailty at 18 mo or older. Colonization of male GF mice increased blood Ly6C^high monocytes, skeletal muscle size, myofiber fiber size, and decreased frailty at 18 mo or older. Transcriptomic analysis of the tibialis anterior muscle revealed a microbiota-muscle axis with over 550 differentially expressed genes in COL male mice at 18 mo or older. Colonized male mice had transcripts indicative of lower tumor necrosis factor (TNF)-α signaling via nuclear factor κB (NF-κB). Our findings show that microbiota can increase systemic cellular immunity while decreasing muscle inflammation, thereby protecting against muscle loss and frailty. We also found sex differences in the role of microbiota regulating frailty. We propose that microbiota components protect against lower muscle mass and frailty across the lifespan in mice.<b>NEW & NOTEWORTHY</b> Germ-free mice had increased frailty, lower muscle mass, and lower circulating inflammatory monocytes. Therefore, lower systemic inflammation coincided with worse frailty and muscle loss. Microbial colonization decreased frailty, restored muscle mass, and increased circulating inflammatory monocytes while lowering transcripts in inflammatory TNF and NF-κB pathways within muscle. Hence, microbiota can increase circulating inflammation but decrease muscle inflammation to protect against frailty. This microbiota-muscle axis should be investigated for therapeutic potential in muscle wasting and sarcopenia.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C887-C894"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Effects of Olaparib and Palbociclib in Resistant epithelial ovarian cancer.","authors":"Shuo Wang, Yan Gao","doi":"10.1152/ajpcell.00481.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00481.2024","url":null,"abstract":"<p><p>This study investigates the mechanisms of poly ADP-ribose polymerase inhibitor (PARPi) resistance in epithelial ovarian cancer (EOC). It also explores strategies to overcome this resistance by combining PARPi with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). EOC cell lines A2780 and SKOV-3 were treated with PARPi to develop stable drug-resistant cell lines, A2780-ola-r and SKOV-3-ola-r. Low-dose treatments with Olaparib, Palbociclib, and their combination significantly reduced tumor proliferation in these resistant cells. Bioinformatics analysis identified potential therapeutic targets, KNSTRN and TRPC4AP. The combination treatment induced G1 phase cell cycle arrest at low drug concentrations. Immunofluorescence studies demonstrated reduced nuclear RAD51 and increased p-γH2AX levels following combination or Palbociclib treatment, compared to DMSO. Western blot analysis revealed elevated expression of homologous recombination repair (HRR) pathway-related proteins in the resistant cell lines. Post-treatment analysis indicated a negative correlation between KNSTRN levels and the efficacy of CDK4/6i or combination therapy, whereas TRPC4AP levels positively correlated with treatment response. These findings offer critical insights into the mechanisms of PARPi resistance in EOC and suggest that combining PARPi with CDK4/6i is a promising therapeutic strategy to overcome this resistance and improve outcomes for patients with EOC.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}