Cell Biology International最新文献

{"title":"Small Extracellular Vesicle-TLN1 Modulates Gastric Cancer Cells and Remodels Lymphatic Endothelial Cells Through AKT Activation to Potentiate Lymphatic Metastasis","authors":"Yuanyuan Li,&nbsp;Jing Wen,&nbsp;Xiaoli Cao,&nbsp;Jiahui Liu,&nbsp;Min Li,&nbsp;Mei Wang,&nbsp;Xin Sha","doi":"10.1002/cbin.70179","DOIUrl":"10.1002/cbin.70179","url":null,"abstract":"<div>\u0000 \u0000 <p>Lymph node metastasis is a pivotal determinant of poor prognosis of gastric cancer, but the molecular orchestrators of lymphatic dissemination remain poorly characterized. Recent research highlights the pivotal role of small extracellular vesicles (sEVs) with specific cargo during the process. Herein, TLN1 was identified as being selectively enriched within sEVs from highly lymph-metastatic gastric cancer cells and in the serum of gastric cancer patients with lymph node metastasis, as identified through proteomic screening and confirmed by western blotting. sEVs act as key autocrine signals that influence gastric cancer cell behaviors such as proliferation, migration, invasion, and adhesion. TLN1 protein levels in cells correlate with their lymphatic metastatic potential and determine TLN1 content in sEVs. Inhibiting TLN1 reduces these cancer cell malignant behaviors and leads to TLN1-depleted sEVs. TLN1 could be transferred to gastric cancer cells and human lymphatic endothelial cells (HLECs) via sEVs. Without TLN1, sEVs cannot enhance cancer cell malignancy or induce HLEC proliferation, tube formation, adhesion, permeability in vitro, or lymphatic metastasis in vivo. Mechanistically, AKT activation was identified as a mediator of the effects exerted by sEV-TLN1 on both gastric cancer cells and HLECs. In conclusion, TLN1 orchestrates lymphatic metastasis in gastric cancer by dual-modulating tumor cell malignancy and lymphatic vessel remodeling via AKT activation. This discovery offers new perspectives on the mechanisms driving lymphatic metastasis in gastric cancer and proposes a promising target for the detection and therapeutic intervention of lymph node metastasis.</p></div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria-Associated Endoplasmic Reticulum Membranes in Cancer: Hubs for Tumor Progression and Therapeutic Vulnerabilities","authors":"Linlin Yan,&nbsp;Shaoqing Liu,&nbsp;Kai Wu,&nbsp;Ming Gao,&nbsp;Dan Yan,&nbsp;Meiling Tian,&nbsp;Jing Xiao,&nbsp;Yang Yang,&nbsp;Bo Qin","doi":"10.1002/cbin.70185","DOIUrl":"https://doi.org/10.1002/cbin.70185","url":null,"abstract":"<div>\u0000 \u0000 <p>Mitochondria-associated endoplasmic reticulum membranes (MAMs) are dynamic contact sites between the endoplasmic reticulum (ER) and mitochondria that coordinate multiple cellular processes such as calcium signaling, lipid trafficking, and redox homeostasis. Increasing evidence shows that cancer cells remodel MAMs to support metabolic adaptation, stress tolerance, tumor progression, and therapeutic resistance. In this review, we summarize the structural organization of MAMs, the core tethering and regulatory mechanisms governing their plasticity, and emerging evidence linking MAM dysfunction to malignant phenotypes and therapeutic resistance. We highlight that the roles of MAM-associated proteins in cancer are highly context-dependent, varying with tumor type, metabolic state, and therapeutic pressure. We further discuss emerging therapeutic strategies targeting MAM-associated pathways, as well as combination approaches to overcome resistance. A better mechanistic understanding of MAM remodeling may reveal actionable vulnerabilities and support biomarker-guided precision therapy across cancer types.</p></div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148386661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose-Derived Stem Cells Differentiate Into Insulin-Producing Cells in 2D Culture With Photobiomodulation: A Comparative Analysis of Wavelength and Fluence Parameters","authors":"O. Daramola,&nbsp;H. Abrahamse,&nbsp;A. Crous","doi":"10.1002/cbin.70182","DOIUrl":"10.1002/cbin.70182","url":null,"abstract":"<p>Diabetes mellitus is a chronic metabolic disorder characterized by the loss or dysfunction of insulin-producing beta (β) cells. Adipose-derived stem cells (ADSCs) represent a promising source for generating functional insulin-producing β cells due to their accessibility and differentiation potential. Photobiomodulation (PBM), a non-invasive light-based therapy, has emerged as an innovative strategy to enhance stem cell differentiation efficiency. Evidence suggests that green (525 nm) and near-infrared (825 nm) wavelengths, applied individually or in combination, can modulate cellular metabolism, ATP production, and differentiation-related signaling pathways, thereby influencing ADSC commitment toward insulin-producing β-cell-like phenotypes. This in vitro study evaluated the effects of PBM at 525 nm and 825 nm, delivered individually and in combination at energy fluences of 5 J/cm² and 10 J/cm², on the differentiation of ADSCs cultured in β-cell induction medium into insulin-producing β-cell-like cells under two-dimensional (2D) culture conditions at 24 h, 5 days, and 10 days. Cellular responses were evaluated using adenosine triphosphate (ATP) luminescence assays, lactate dehydrogenase (LDH) activity assays, Giemsa staining, Live/Dead viability assays, and dithizone (DTZ) staining. ATP levels varied significantly among the experimental groups, reflecting changes in cellular metabolic activity associated with β-cell induction and PBM exposure, and reduced LDH activity, suggesting decreased cytotoxicity. Giemsa staining revealed morphological changes consistent with β-cell differentiation, while Live/Dead assays demonstrated the maintenance of cell viability across all experimental groups. Dithizone staining identified the presence of zinc-rich insulin-producing clusters. These findings highlight the importance of PBM wavelength and fluence optimization in regenerative stem cell applications.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbin.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Neurosphere Formation as a Functional Readout of Aberrant EGFR Signaling Kinetics in Olfactory Neural Progenitors From Patients With Schizophrenia","authors":"Tommaso Toffanin,&nbsp;Mario Angelo Pagano,&nbsp;Carlo Idotta,&nbsp;Mauro Salvi,&nbsp;Valentina Bosello-Travain,&nbsp;Maria Lina Massimino,&nbsp;Roberto Saetti,&nbsp;Marina Silvestrini,&nbsp;Leonardo Meneghetti,&nbsp;Stefano Piazza,&nbsp;Maria Giulia Nanni,&nbsp;Rosangela Caruso,&nbsp;Maria Ferrara,&nbsp;Chiara Montemitro,&nbsp;Luigi Zerbinati,&nbsp;Martino Belvederi Murri,&nbsp;Luigi Grassi,&nbsp;Anna Maria Brunati","doi":"10.1002/cbin.70181","DOIUrl":"10.1002/cbin.70181","url":null,"abstract":"<p>The Epidermal Growth Factor Receptor (EGFR) is a key regulator of neurodevelopment, controlling the proliferation, differentiation, and self-renewal of neural stem and progenitor cells. Dysregulated EGFR signaling has been implicated in schizophrenia, a neurodevelopmental disorder associated with abnormal cortical maturation. We investigated EGFR-dependent signaling in neural stem/progenitor cells derived from olfactory neuroepithelium (hereafter referred to as Olfactory Neural Stem/Progenitor Cells, ONSPCs) collected from individuals with no prior history of psychiatric disorders (hereafter referred to as healthy controls, HC) and patients diagnosed with schizophrenia (schizophrenic, SZ), an ex vivo human model that retains disease-related molecular signatures. Both HC- and SZ-derived ONSPCs formed neurospheres under proliferative conditions in the presence of the growth factors Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF), confirming their neural progenitor identity. However, under EGF-exclusive conditions, HC-derived ONSPCs generated compact, well-organized neurospheres, whereas SZ-derived ONSPCs produced sparse, irregular aggregates, indicating impaired responsiveness to EGF. Despite comparable EGFR protein levels between groups, EGF stimulation revealed distinct dynamics of downstream EGFR effectors. In HC-derived ONSPCs, EGFR activation was initially modest but sustained over time, whereas in SZ-derived cells it was more rapid and transiently stronger, followed by early signal decay. In particular, Akt and Src, which are implicated in signaling pathways driving proliferation and self-renewal, displayed activation dynamics paralleling those of EGFR in each group. These findings are consistent with dysregulation of the magnitude and temporal dynamics of EGFR–dependent signaling in SZ-derived ONSPCs, associated with impaired neurosphere formation under EGF-exclusive conditions and suggestive of reduced self-renewal capacity. Although limited by the modest sample size, the semiquantitative nature of Western blot analyses, and the potential effect of medication exposure, this study supports the relevance of patient-derived ONSPCs as a physiologically meaningful platform for investigating neurodevelopmental mechanisms underlying schizophrenia.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbin.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanobiology-Driven Metabolic Reprogramming: Integrative Roles of YAP/TAZ Signaling and Extracellular Matrix Dynamics","authors":"Arul Narayanasamy,&nbsp;Panimalar Abirami Karuppusamy,&nbsp;Roselin Gnanarajan,&nbsp;Nandita Ravichandran,&nbsp;Deenathayalan Uvarajan,&nbsp;Mahalaxmi Iyer,&nbsp;Jayalakshmi Krishnan,&nbsp;Jyoti Parkash,&nbsp;Dibbanti Harikrishnareddy,&nbsp;Adhiyaman Muniraj,&nbsp;Shreshta Vidhya Elango,&nbsp;Saranya Vinayagam,&nbsp;Lalitha Gnanasekaran,&nbsp;Anirban Goutam Mukherjee,&nbsp;Balachandar Vellingiri,&nbsp;Raja Ganesan","doi":"10.1002/cbin.70180","DOIUrl":"10.1002/cbin.70180","url":null,"abstract":"<div>\u0000 \u0000 <p>Mechanobiology has emerged as a critical regulator of cellular metabolism, linking physical forces to transcriptional, metabolic, and epigenetic adaptations across multiple organ systems. However, the mechanisms by which extracellular matrix (ECM) dynamics and mechanotransduction pathways coordinate metabolic reprogramming in physiological and pathological conditions remain incompletely understood. This review provides a focused mechanometabolic framework integrating cardiovascular, skeletal, and endocrine systems through the convergence of ECM remodeling, cytoskeletal tension, and force-dependent signaling pathways. Central to this framework is the YAP/TAZ signaling axis, which functions as a mechanosensitive transcriptional regulator downstream of integrin-focal adhesion kinase (FAK)-Src, RhoA/ROCK, actomyosin tension, and Hippo-dependent and Hippo-independent signaling networks. These pathways regulate metabolic programs involving glycolysis, mitochondrial function, redox homeostasis, and anabolic biosynthesis through downstream targets including GLUT1, HK2, PFKFB3, and mitochondrial regulatory pathways. The review critically examines how aberrant mechanotransduction contributes to cardiovascular remodeling, endothelial dysfunction, fibrosis, and metabolic disease progression, while also discussing the context-dependent roles of YAP/TAZ signaling in adaptive versus pathological responses. In skeletal metabolism, the gut-bone axis is presented as a bidirectional mechanochemical network in which microbiota-derived metabolites, osteoimmune signaling, and biomechanical loading coordinately regulate bone remodeling and systemic metabolism. Furthermore, the review evaluates emerging evidence linking viscoelasticity, mitochondrial dynamics, and immunometabolism to disease progression and therapeutic responsiveness. Advances in mechanobiomaterials and regenerative strategies are also discussed, emphasizing their ability to modulate cellular energetics and mechanotransduction pathways to restore tissue homeostasis. Finally, current limitations in mechanobiology research, including model heterogeneity, tissue-specific mechanical responses, and translational barriers, are highlighted. Collectively, this review establishes mechanobiology as a systems-level regulator of metabolic reprogramming and underscores the therapeutic potential of targeting mechanometabolic pathways in human disease.</p></div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NPC2 Regulates Glioblastoma Cholesterol Metabolism and Malignant Behavior via GPX4-Linked Ferroptosis","authors":"Wei Jiang,&nbsp;Wei Wang,&nbsp;Junping Wang,&nbsp;Fan Xia,&nbsp;Guoyu Wang,&nbsp;Hongzhi Wang,&nbsp;Xueran Chen,&nbsp;Zhiyou Fang","doi":"10.1002/cbin.70184","DOIUrl":"https://doi.org/10.1002/cbin.70184","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma (GBM) is a highly aggressive intracranial malignancy originating from neuroepithelial glial progenitors. The prominent intra- and intertumoral heterogeneity of GBM is a major driver of therapeutic resistance and frequent tumor recurrence. Cholesterol is an essential structural component of mammalian cell membranes and plays crucial roles in membrane trafficking and transmembrane signal transduction. As a key intracellular cholesterol transporter, the Niemann-Pick type C2 (NPC2) protein remains poorly characterized regarding its biological functions and clinical implications in GBM. In this study, immunohistochemical staining of clinical GBM specimens revealed that elevated NPC2 expression was significantly correlated with unfavorable patient prognosis. Consistent with clinical observations, genetic knockdown of NPC2 markedly suppressed the proliferation and invasion abilities of LN18 cells. Mechanistically, NPC2 silencing downregulated GPX4 expression at both transcriptional and translational levels, suggesting a potential regulatory relationship between NPC2 and the ferroptosis pathway. Collectively, these findings indicate that NPC2 may facilitate GBM malignant progression partially through modulating GPX4-mediated ferroptosis, thereby representing a tentative prognostic biomarker and a potential therapeutic target for GBM that requires further validation.</p></div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148322369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin as a Modulator of Cancer Cell Biology: Integrated Control of Proliferation, Cell Death Programs, Metastasis Signaling, and Delivery Challenges","authors":"Putri Cahaya Situmorang,&nbsp;Cheryl Grace Pratiwi Rumahorbo,&nbsp;Alexander Patera Nugraha,&nbsp;Zainab M. Almarhoon,&nbsp;William N. Setzer,&nbsp;Javad Sharifi-Rad","doi":"10.1002/cbin.70174","DOIUrl":"10.1002/cbin.70174","url":null,"abstract":"<div>\u0000 \u0000 <p>Icariin, a prenylated flavonoid derived from plants of the <i>Epimedium</i> genus, has attracted increasing attention due to its broad spectrum of pharmacological activities, particularly its anticancer potential. Accumulating evidence indicates that icariin exerts strong inhibitory effects on tumor initiation, progression, and metastasis through modulation of multiple cellular and molecular pathways. Icariin regulates critical signaling cascades, including PI3K/AKT, MAPK, Wnt/β-catenin, and NF-κB, leading to the suppression of proliferation, induction of apoptosis, inhibition of angiogenesis, and reversal of multidrug resistance. Furthermore, icariin demonstrates the ability to modulate tumor immune responses and enhance the efficacy of conventional chemotherapeutic and radiotherapeutic regimens. Preclinical studies across diverse cancer models, such as breast, prostate, colorectal, and lung cancers, consistently highlight its therapeutic promise. Despite these encouraging results, limitations remain regarding its poor bioavailability and pharmacokinetic profile. Recent advances in nanotechnology-based drug delivery systems have shown potential to overcome these challenges, improving stability, absorption, and targeted delivery. Collectively, current findings underscore icariin as a multifunctional natural compound with significant promise for cancer prevention and therapy. Future research should focus on well-designed clinical studies and innovative delivery strategies to fully translate its anticancer potential into clinical applications.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RPL27 Promotes Gastric Cancer Progression by Enhancing Oxidative Phosphorylation Via FMC1","authors":"Yan Zheng,&nbsp;Yuhui Ye,&nbsp;Yang Cheng,&nbsp;Minzhi Sun,&nbsp;He Yu,&nbsp;Chuiping Zeng,&nbsp;Lijun He,&nbsp;Hui Zhang,&nbsp;Fengsong Wang,&nbsp;Zhen Lu","doi":"10.1002/cbin.70178","DOIUrl":"10.1002/cbin.70178","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric cancer remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for novel biomarkers and therapeutic targets. Ribosomal proteins have recently emerged as critical regulators of tumorigenesis beyond their classical roles in protein synthesis. Here, we investigated the expression, functional significance, and underlying mechanism of RPL27 in gastric cancer. RPL27 was markedly upregulated in gastric cancer tissues compared with adjacent normal tissues, as demonstrated by Western blotting and immunohistochemistry. High RPL27 expression was significantly associated with poor overall survival, suggesting its potential as a prognostic biomarker. Functional assays revealed that RPL27 knockdown substantially suppressed gastric cancer cell proliferation, migration, and invasion. Transcriptomic analysis identified FMC1 as a key downstream molecule of RPL27, mediating its regulatory effects on mitochondrial function, including alterations in membrane potential, morphology, DNA copy number, and ATP5A expression. Rescue experiments demonstrated that either FMC1 knockdown or treatment with the OXPHOS inhibitor oligomycin A partially reversed the malignant phenotypes induced by RPL27 overexpression. Furthermore, RPL27 knockdown significantly inhibited tumor growth in a xenograft mouse model. Collectively, these findings establish RPL27 as a novel oncogenic driver in gastric cancer and demonstrate that it promotes tumor progression through FMC1-dependent regulation of oxidative phosphorylation. The RPL27-FMC1-mitochondrial function axis may thus represent a promising vulnerability for therapeutic intervention in gastric cancer.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Lysophosphatidic Acid Supplementation Enhances Megakaryocyte Differentiation and Platelet Production From Human Hematopoietic Progenitors","authors":"Nittaya Jiamvoraphong,&nbsp;Chanchao Lorthongpanich,&nbsp;Praphasri Septham,&nbsp;Phatchanat Klaihmon,&nbsp;Pakpoom Kheolamai,&nbsp;Chuti Laowtammathron,&nbsp;Sumeth Imsoonthornruksa,&nbsp;Mariena Ketudat-Cairns,&nbsp;Surapol Issaragrisil","doi":"10.1002/cbin.70177","DOIUrl":"10.1002/cbin.70177","url":null,"abstract":"<p>Platelet shortages and limited storage stability restrict global platelet transfusion capacity, highlighting the need for efficient in vitro platelet production systems. This study establishes a simple, non-genetic and cost-effective system for efficient in vitro platelet-like particle (PLP) production from human hematopoietic stem/progenitor cells (HSPCs) using a Phase-specific modulation of Hippo-YAP/TAZ signaling modulation. Temporal control of Hippo-YAP/TAZ signaling by lysophosphatidic acid (LPA), an activator of YAP/TAZ activity, significantly enhanced megakaryocyte differentiation, expansion and PLP production, resulting in an approximately 15-fold increase in PLP yield at the end of the procedure. Furthermore, LPA extended the expansion period of HSPC-derived megakaryocytes up to 8 days, resulting in a greater than 20-fold increase in the number of HSPC-derived CD41⁺ megakaryocytes. Moreover, replacement of expensive commercial recombinant human thrombopoietin (C-rhTPO), one of the major cost-driving components in in vitro PLP production, with recombinant human thrombopoietin produced in <i>Escherichia coli</i> (W-rhTPO) further improved the cost-effectiveness of the procedure. In conclusion, this study demonstrates that temporally controlled Hippo-YAP/TAZ signaling, together with affordable cytokine supplementation, provides a robust and GMP-compatible platform for large-scale PLP manufacturing for future clinical applications. We believe that this system will enable scalable PLP generation, even in resource-constrained settings, to increase human platelet supply for many life-saving therapies in the future.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbin.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Karyopherin Subunit Alpha 3 Drives Temozolomide Resistance in Glioblastoma by Upregulating MGMT and Activating STAT3 to Sustain Glioma Stem Cells","authors":"Yanru Gao,&nbsp;He Yuan,&nbsp;Houling Zhou,&nbsp;Chao Gao,&nbsp;Suling Sun,&nbsp;Chuanjie He,&nbsp;Zhiyou Fang,&nbsp;Xueran Chen","doi":"10.1002/cbin.70175","DOIUrl":"10.1002/cbin.70175","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma (GBM) invariably develops resistance to temozolomide (TMZ), the frontline chemotherapeutic agent, leading to treatment failure. The molecular mechanisms underlying this resistance remain incompletely understood. Here, we identify karyopherin subunit alpha 3 (KPNA3) as a potential contributor to TMZ resistance. Through integrated bioinformatics analysis of TMZ-resistant glioma cells (SF126R) and patient databases, we found KPNA3 expression is elevated in TMZ-resistant contexts and correlates with poor prognosis in TMZ-treated patients. Functional studies demonstrated that KPNA3 knockdown in resistant cells impaired malignant behaviors, re-sensitized cells to TMZ-induced apoptosis, and suppressed glioma stem cell (GSC) properties, including sphere formation and expression of stemness factors (OCT4, ALDH1A1). Mechanistically, KPNA3 was associated with a dual pathway: it correlated with increased expression of the DNA repair enzyme MGMT and was linked to activation of the STAT3 signaling pathway. KPNA3 knockdown reduced both MGMT levels and STAT3 phosphorylation (Tyr705). Furthermore, pharmacological inhibition of STAT3 mirrored the effect of KPNA3 knockdown by potently inhibiting GSC generation. Clinically, KPNA3 and <i>p</i>-STAT3 protein levels were positively correlated in high-grade glioma tissues. Collectively, our findings suggest that KPNA3 may play a role in concurrently enhances DNA repair and sustains the GSC population to foster TMZ resistance, identifying it as a candidate for further investigation for overcoming chemoresistance in GBM.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}