Biology of the Cell最新文献

{"title":"ZDHHC7 Promotes Pyroptosis and Inhibits Breast Cancer Progression by Palmitoylating NLRP3","authors":"Ke Tang,&nbsp;Ya Hu,&nbsp;Fangting Tang,&nbsp;Maoliang Xiao","doi":"10.1111/boc.70083","DOIUrl":"10.1111/boc.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer (BrCa) has become the most common malignant tumor among women worldwide. Inducing tumor cell pyroptosis has emerged as a potential anti-tumor strategy, although the biological effects of pyroptosis are context-dependent and may be dual-edged. The NLRP3 inflammasome is a major regulator of canonical pyroptosis. However, the role of ZDHHC7-mediated NLRP3 palmitoylation in BrCa remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ZDHHC7 expression was analyzed using UALCAN, Kaplan-Meier plotter, qPCR, and Western blotting. The growth and metastasis ability of cells were detected and evaluated, respectively, using the CCK-8 method and the Transwell assay. Pyroptosis was evaluated through Western blot, ELISA, and flow cytometry. NLRP3 palmitoylation was examined by acyl-biotin exchange (ABE) assay. Tumor growth was evaluated in xenograft models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with normal controls, ZDHHC7 is characterized by low expression in BrCa, and its low expression level is related to a decreased survival rate of patients. ZDHHC7 overexpression suppressed proliferation, migration, and invasion. Furthermore, ZDHHC7 overexpression promoted NLRP3 palmitoylation, activating the NLRP3 inflammasome, which increased levels of cleaved Caspase-1 and GSDMD-N, elevated secretion of IL-1β, IL-18, and LDH, and induced pyroptosis. These effects were partially reversed by NLRP3 inhibitor. Functional rescue experiments confirmed that NLRP3 inhibition restored the malignant phenotypes suppressed by ZDHHC7. In vivo, ZDHHC7 or NLRP3 overexpression inhibited tumor growth, reduced Ki67 expression, and increased pyroptosis markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ZDHHC7 may function as a tumor suppressor in BrCa by promoting NLRP3 palmitoylation, thereby activating NLRP3 inflammasome-mediated pyroptosis and inhibiting malignant progression in experimental models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Extracellular Vesicles From Cancer Cells in Acidosis or ER Stress to Endothelial Cells: Angiogenesis and Endothelial Activation","authors":"Ana Sayuri Yamagata,&nbsp;Ramon H. G. Teles,&nbsp;Nicolas J. Villarinho,&nbsp;Ana Carolina Lima Ralph,&nbsp;Nicolly C. dos Santos,&nbsp;Kevin Perera,&nbsp;Gisela R. Terçarioli,&nbsp;Amanda Ikegami,&nbsp;Anayara Ristow,&nbsp;Daniel Pecoraro Demarque,&nbsp;Jeremy Newton,&nbsp;Luiz E. da Silva,&nbsp;Edmond W. K. Young,&nbsp;Ruy G. Jaeger,&nbsp;Vanessa Morais Freitas","doi":"10.1111/boc.70085","DOIUrl":"10.1111/boc.70085","url":null,"abstract":"<p>Tumor-derived extracellular vesicles (EVs) facilitate metastatic progression by transferring bioactive cargo to recipient cells, thereby increasing endothelial permeability and promoting angiogenesis. The harsh conditions of the tumor microenvironment, such as extracellular acidosis, can alter the content of EVs, leading to changes in recipient cells, including endoplasmic reticulum (ER) stress. This study aimed to investigate whether EVs released by tumor cells adapted to acidosis or ER stress can alter endothelial functional properties. ER stress was induced in MDA-MB-231 breast cancer cells with tunicamycin, and adaptation to acidosis was achieved by culturing at pH 6.5 for 30 days. Large extracellular vesicles (LEVs) in these conditions were isolated by centrifugation. LEVs were characterized by nanoparticle tracking analysis (NTA), immunogold, Western blot, and high-performance liquid chromatography (HPLC). ER stress and autophagy markers were quantified by Western blot; cancer cells' adhesion to endothelial cells was assessed by adhesion assay; barrier permeability by dextran diffusion in an organ-on-a-chip model; migration by wound healing assay, and angiogenesis by tube formation assay. Tunicamycin was not detected in LEV from tunicamycin-treated cells (LEV T). LEV T increased the migration of endothelial cells, while not inducing ER stress, nor altering adhesion, angiogenesis, or permeability. Acidosis-adapted cells did not have greater UPR activation, but their LEVs (LEV 6.5) induced ER stress, reduced adhesion and angiogenesis, and increased permeability and migration. These findings indicate that LEVs from acidosis-adapted tumor cells reprogram endothelial physiology, supporting a potential role in metastatic progression.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Extracellular Vesicles in Shaping Immune Responses in the Lymph Node Microenvironment","authors":"Alicia Charrier,&nbsp;Apolline Salama,&nbsp;Laurence Dubreil,&nbsp;Grégoire Mignot,&nbsp;Steffi Bosch","doi":"10.1111/boc.70084","DOIUrl":"10.1111/boc.70084","url":null,"abstract":"<p>Extracellular vesicles (EV) secreted by living cells are important players in cell-to-cell communication, particularly in the diffuse immune system, where they contribute to local and systemic coordination. Indeed, EV are in the ideal size range for diffusion in interstitial and lymphatic fluids, which is the main route of tissue EV trafficking towards secondary lymphoid organs that orchestrate immune responses. In the lymph nodes, EV interact with multiple immune and stromal cell populations sensitive to antigens and co-delivered tissue messages via degradative and non-degradative pathways. Natural conveyers of bioactive compounds inherited from their mother cells and their surroundings, EV modulate innate and adaptive immune responses in health and disease. The aim of this scoping review is to aggregate information from the literature on cellular effectors and molecular pathways of EV-mediated immune responses in the lymph node environment and to gain insight into practices using EV for immune intervention\u0000.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Underexplored Mechanobiology of Lamin A Biogenesis and Homeostasis","authors":"Sandrine Fraboulet,&nbsp;Omar Aldarawish,&nbsp;Monika Elzbieta Dolega","doi":"10.1111/boc.70080","DOIUrl":"10.1111/boc.70080","url":null,"abstract":"<p>Lamin A is a major contributor to nuclear mechanics and an important mediator of mechanotransduction. While its role in regulating nuclear architecture is well established, considerably less attention has been given to how mechanical cues regulate lamin A itself. Here, we review current evidence demonstrating that lamin A homeostasis is dynamically controlled by mechanical stimulation through transcriptional, translational, and post-translational mechanisms regulating protein abundance, stability, and turnover. We further discuss emerging evidence suggesting that prelamin A maturation, a highly conserved multistep processing pathway, may represent a previously unrecognized mechanosensitive regulatory node. Recent studies challenge the canonical model of prelamin A processing and raise the possibility of alternative maturation pathways with important implications for lamin A homeostasis. We highlight current evidence, unresolved questions, and future directions, proposing that mechanical regulation of lamin A biogenesis represents an underexplored dimension of lamin mechanobiology with broad implications for development, aging, laminopathies, and mechanically driven diseases.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Inhibitory Effect of Manumycin A on Extracellular Vesicles: What Do We Know So Far?","authors":"Agata Abramowicz","doi":"10.1111/boc.70081","DOIUrl":"https://doi.org/10.1111/boc.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>Manumycin A (MA) is a natural antibiotic produced by <i>Streptomyces parvulus</i>, originally reported as a selective Ras farnesyltransferase inhibitor. Over the years, it has been established as a valuable agent in the studies of the molecular biology of cancer. Recent interest in the use of MA as an inhibitor of extracellular vesicles (EV) shows new perspectives for this small molecule in view of the urgent need for effective molecular tools for this application. This review summarizes the current knowledge on Manumycin A, with a particular focus on its potential utility in EV-related biomedical studies. The inhibitory mechanism and possible application limitations are discussed, and current results of studies involving MA have been presented. Conclusions include remarks that the actual cellular response can vary depending on cell type and dose, and due to the risk of cytotoxic effects, MA requires a cautious approach. Although available data indicate that Manumycin A may be considered to be used as an inhibitor of extracellular vesicles, the exact mechanism of action still requires further comprehensive investigation. Therefore, it would be desirable for any study that uses Manumycin A as an inhibitor to also include a thorough characterization of the effect of the dose on cells and extracellular vesicles using various research techniques.</p>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Striated Membrane Contact Site in Vestibular Hair Cells","authors":"Nicolas Brouilly,&nbsp;Nathalie Pujol,&nbsp;Fabrice Richard,&nbsp;Chantal Cazevieille,&nbsp;Jennifer Stone,&nbsp;Ruth Anne Eatock,&nbsp;Rémy Pujol","doi":"10.1111/boc.70082","DOIUrl":"https://doi.org/10.1111/boc.70082","url":null,"abstract":"<p>The mammalian vestibular system has two types of sensory receptor hair cells (HCs), each with different neurotransmission mechanisms. Type II HCs use ribbon synapses to transmit neurotransmitters like glutamate to bouton terminals of afferent neurons. Type I HCs are nearly engulfed by a calyceal afferent ending. They regulate afferent activity through both quantal and non-quantal transmission (NQT), the latter faster than classic neurotransmitter release and potentially key to stabilizing vision and balance during rapid head movements. Here, we describe a novel striated contact, present only in the mouse type I HC and its calyceal afferent ending. Electron tomography reveals periodic striations on both the HC and calyx plasma membranes. These contact sites are intimately associated with a plasma membrane mitochondria contact site on the type I HC side of the synapse. Given that mitochondrion–plasma membrane contact sites in other systems regulate local ion homeostasis, this distinctive arrangement has the potential to serve or modulate NQT at the type I HC–calyx synapse.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Streamlined Workflow for the Isolation of Bovine Satellite Cells From Muscle Tissue","authors":"Tobias Horst Baldeweg,&nbsp;Svenja Nellinger,&nbsp;Anna Leikeim,&nbsp;Simon Heine,&nbsp;Petra Juliane Kluger","doi":"10.1111/boc.70079","DOIUrl":"https://doi.org/10.1111/boc.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Satellite cells are the primary drivers of skeletal muscle growth and regeneration and are a major cell source in both muscle tissue engineering and cultivated meat. However, current bovine satellite cell isolation can be technically demanding or yield heterogeneous cell populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study presents a workflow optimized for simplicity and cost-efficiency by integrating rapid muscle processing using electric mincing with magnetic-activated cell sorting targeting Integrin-α7 to reliably enrich satellite cells. The isolated cells were characterized by Pax7 immunostaining and myogenic differentiation assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ITGA7-based magnetic sorting yielded an enriched satellite cell population corresponding to 49.39 ± 14.70 × 10³ cells per gram of minced tissue. The isolated cells exhibited high Pax7 expression (98 ± 1.34% Pax7-positive cells) and strong myogenic differentiation capacity (differentiation index: 94.39 ± 3.58%), confirming their identity and functional potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By minimizing hands-on effort and avoiding specialized equipment, this workflow lowers technical and financial barriers while enabling the acquisition of highly enriched, early-passage satellite cell populations. This workflow provides an adaptable foundation for advancing cultivated meat bioprocess development and accelerating research in skeletal muscle biology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AP-1B Controls Several Levels of Cell Proliferation and Differentiation in Mouse Enteroids","authors":"Maela Duclos,&nbsp;Anne Bourdais,&nbsp;Ophélie Nicolle,&nbsp;Alexandre Helpiquet,&nbsp;Grégoire Michaux,&nbsp;Aurélien Bidaud-Meynard","doi":"10.1111/boc.70076","DOIUrl":"https://doi.org/10.1111/boc.70076","url":null,"abstract":"<p>Gut homeostasis relies on the tightly controlled balance between intestinal stem cell self-renewal and differentiation. The clathrin adaptor complex AP-1B plays a pivotal role in establishing the polarity of enterocytes as well as in the asymmetric distribution of membrane proteins, including the brush border transporters that govern intestinal absorption. Additionally, AP-1B has been involved in the control of intestinal cell proliferation, which suggests that it may regulate various aspects of gut functional organisation. In this study, we investigated the consequences of conditional mutations of the gene encoding the AP-1B subunit μ1B (<i>Ap1m2</i>) in mouse enteroids. We first showed in this model that <i>Ap1m2</i> mutations also induce strong polarity defects at the subcellular level in the absorptive enterocytes. Next, we unveiled that AP-1B regulates intestinal cell differentiation at the tissular level, through the commitment of stem/progenitor cells towards the secretory lineage and cell positioning along the crypt-villus axis. Furthermore, we showed that AP-1B inhibition also induces hyperproliferation in enteroids. Notably, we unravelled that, complementary to the Wnt/<i>β</i>-catenin-mediated proliferation described in <i>null</i> mice, AP-1B downregulation triggers a tissue-autonomous, mTOR/YAP-dependent, proliferative pathway. Overall, these results enlighten the pleiotropic roles played by AP-1B in the homeostasis of the gut epithelium.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress and Nrf2 Signaling Role in Oral Squamous Cell Carcinoma: A Double-Edged Sword","authors":"Ashraf Ullah Khan,&nbsp;Adnan Khan,&nbsp;Bushra Shal,&nbsp;Salman Khan,&nbsp;Sarah Sarwar,&nbsp;Jamshid Ullah,&nbsp;Amin Ullah,&nbsp;Kannan RR Rengasamy","doi":"10.1111/boc.70073","DOIUrl":"https://doi.org/10.1111/boc.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress has a significant role in the origination and progression of oral squamous cell carcinoma (OSCC) by interrupting cellular redox homeostasis and gene regulation. The nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway is a major regulator of antioxidant defense, activating cytoprotective genes under stress conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The study highlight the dual role of the Kelch-like ECH-associated protein-1 (Keap1)/Nrf2 signaling pathway in the development, progression, and therapeutic resistance of OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Literature was conducted to evaluate the role of oxidative stress and Keap1/Nrf2 signaling in OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nrf2 protects normal cells from oxidative damage, its persistent activation in cancer cells promotes tumor progression, metabolic reprogramming, and resistance to chemotherapy and radiotherapy. Dysregulation of the Keap1/Nrf2 axis enhances cancer cell survival and contributes to radioresistance in OSCC. However, Nrf2 displays a dual function as both a tumor suppressor and promoter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The Keap1/Nrf2 signaling pathway plays a key role in OSCC pathogenesis and treatment resistance. Targeting the Keap1/Nrf2 signaling pathway may provide a promising therapeutic strategy to overcome treatment resistance in OSCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt Stimulation and Inhibition in the Development and Phenotype of Patient-Derived Gallbladder Organoids","authors":"Ankita Dutta,&nbsp;Payel Guha,&nbsp;Akshaya Vijayan Selvarajan,&nbsp;Nandita Chowdhury,&nbsp;Pritha Banerjee,&nbsp;Shrabanti Sarkar Ghosh,&nbsp;Archana Kumari Shaw,&nbsp;Debdutta Ganguli,&nbsp;Uma Sunderam,&nbsp;Manas Kumar Roy,&nbsp;Sudeep Banerjee,&nbsp;Rajgopal Srinivasan,&nbsp;Paromita Roy,&nbsp;Vaskar Saha,&nbsp;Anindita Dutta,&nbsp;Dwijit GuhaSarkar","doi":"10.1111/boc.70074","DOIUrl":"https://doi.org/10.1111/boc.70074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gallbladder cancer (GBC) is a highly lethal malignancy with limited experimental models to study disease biology or evaluate therapeutic responses. Although canonical Wnt activation is commonly used for patient-derived organoid (PDO) development and expansion, gallbladder PDOs have also been generated under Wnt-inhibitory conditions. No comparative assessments have determined how Wnt pathway modulation influences gallbladder PDO development, phenotype, or drug response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study systematically compared the impact of canonical Wnt activation (WNT^Act medium containing CHIR99021) versus inhibition (WNT^Inh medium containing DKK1) on the establishment, propagation, molecular features, and therapeutic responses of PDOs generated from malignant or non-malignant gallbladder tissues derived from the same patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both media supported successful PDO generation with comparable efficiency, preserving biliary epithelial functions and marker expression. Transcriptomic profiling confirmed selective enrichment of canonical Wnt target genes in PDOs generated in WNT^Act cultures. WNT^Act conditions enabled markedly superior long-term propagation, whereas WNT^Inh cultures more consistently retained the dysplastic features in malignant samples. Gemcitabine response assays demonstrated significantly greater drug sensitivity in PDOs grown in WNT^Act medium, a phenotype reversible upon media switching but requiring extended adaptation, indicating a dynamic and context-dependent influence of Wnt-signaling on chemotherapeutic vulnerability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, the findings reveal a trade-off between long-term propagation and histological fidelity in gallbladder PDOs and show that Wnt-signaling modulates gemcitabine sensitivity in a reversible manner. This comparative framework provides practical guidance for selecting culture conditions for gallbladder PDO-based disease modeling, and precision oncology applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"118 7","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}